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Journal articles on the topic 'Intratumoral CD8 T cells'

Author: Grafiati

Published: 1 February 2025

Last updated: 31 July 2025

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1

Yang, Zhi-Zhang, Anne J. Novak, Mary J. Stenson, Thomas E. Witzig, and Stephen M. Ansell. "Intratumoral Treg Cells Completely Inhibit the Induction and Function of Tumor-Infiltrating CD8+ T-Cells in B-Cell NHL." Blood 106, no. 11 (2005): 3311. http://dx.doi.org/10.1182/blood.v106.11.3311.3311.

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Abstract Background: Numerous studies have shown that lymphoma B-cells are resistant to CTL-mediated death, however the underlying mechanism for this resistance is not clear. In previous work, we have identified a subset of CD4+CD25+ T-cells overrepresented in the tumor sites of B-cell NHL that display a phenotype compatible with regulatory T cells (Treg cells). These cells express high levels of Foxp3 and CTLA-4, and are capable of suppressing the proliferation and cytokine production of autologous infiltrating CD4+CD25- T cells in B-cell NHL. Goal: To explore whether Treg cells exert a suppr

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De Logu, Francesco, Francesca Galli, Romina Nassini, et al. "Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients." Cells 10, no. 2 (2021): 422. http://dx.doi.org/10.3390/cells10020422.

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Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM. Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a train

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Wang, Li-Xin, Suyu Shu, Mary L. Disis, and Gregory E. Plautz. "Adoptive transfer of tumor-primed, in vitro–activated, CD4+ T effector cells (TEs) combined with CD8+ TEs provides intratumoral TE proliferation and synergistic antitumor response." Blood 109, no. 11 (2007): 4865–76. http://dx.doi.org/10.1182/blood-2006-09-045245.

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Abstract The importance of CD4+ Th1 cells during the effector phase of the antitumor response has been overshadowed by emphasis on CD8+ cytotoxic T lymphocytes (CTLs). To determine their respective functions, we purified antigen-primed T cells from tumor-draining lymph nodes and separately activated CD4+ and CD8+ subsets in vitro. Adoptive transfer of CD4+ T effector cells (TEs) combined with CD8+ TEs provided synergistic therapy for mice bearing subcutaneous, intracranial, or advanced pulmonary metastases. CD4+ TEs augmented IFN-γ production by CD8+ TEs when cells were stimulated by tumor dig

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Fenoglio, Daniela, Liliana Belgioia, Alessia Parodi, et al. "Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28− T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer." Cancers 13, no. 9 (2021): 2234. http://dx.doi.org/10.3390/cancers13092234.

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Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28− T cells, and CD8+CD28−CD127−CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28− T cell

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Yang, Zhi-Zhang, Anne J. Novak, Steven C. Ziesmer, Thomas E. Witzig, and Stephen M. Ansell. "CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25− T cells." Blood 110, no. 7 (2007): 2537–44. http://dx.doi.org/10.1182/blood-2007-03-082578.

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Foxp3 expression was initially thought to be restricted to the CD4+CD25+ regulatory T-cell population. However, recent studies suggest that forkhead box P3 (Foxp3) is expressed in CD4+CD25− T cells in aged mice. In the present study in B-cell non-Hodgkin lymphoma (NHL), we found that a subset of intratumoral but not peripheral blood CD4+CD25− T cells, comprising about 15% of intratumoral CD4+ T cells, express Foxp3 and are capable of suppressing the proliferation of autologous infiltrating CD8+ T cells. In vitro activation with OKT3/anti-CD28 antibody (Ab) or dendritic cells (DCs) induced Foxp

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Dorta-Estremera, Stephanie, Krishna Nookala Sita Mahalakshmi, Ananta V. Yanamandra, et al. "Kinetics of intratumoral T-cell activation during chemoradiation for cervical cancer." Journal of Clinical Oncology 36, no. 5_suppl (2018): 6. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.6.

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6 Background: Limited data in cancer patients have suggested that chemotherapy and radiation impact local and systemic immune cell populations. Radiation therapy (RT) is known to deplete circulating lymphocytes but is thought to increase local antigen presentation. The dynamics of these competing effects on the kinetics of intratumoral infiltration and expansion of activated and immunoregulatory T cells are unknown. Methods: We prospectively evaluated intratumoral immune infiltration during fractionated RT using multi-spectral flow cytometry. Cervical brushings were obtained from 14 patients b

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Yang, Jing, Jing Han, Zhen Jiang, et al. "Inhibition of Aurora-A recruited CD8+ T cells infiltration via mediating IL-10 production of cancer cells." Journal of Immunology 204, no. 1_Supplement (2020): 241.13. http://dx.doi.org/10.4049/jimmunol.204.supp.241.13.

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Abstract It has been shown that approximately 10% of infiltrated CD8+ T cells could be the tumor-specific intratumoral CD8+ T cells in colorectal cancer. While, inhibition of Aurora-A, a member of serine/threonine Aurora kinase family, by alisertib promoted the percentage of infiltrated intratumoral CD8+ T cells. We therefore assumed that targeting Aurora-A could be a therapeutic strategy for recruitment of intratumoral CD8+ T cells. In CT-26 tumor model, blockade of Aurora-A with alisertib slowed the tumor growth in association with an increased infiltration, activation and expansion of intra

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Gao, Qiang, Shuang-Jian Qiu, Jia Fan, et al. "Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection." Journal of Clinical Oncology 25, no. 18 (2007): 2586–93. http://dx.doi.org/10.1200/jco.2006.09.4565.

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Purpose To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. Patients and Methods CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. Results CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease

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Dimitrova, Polina, Mariela Vasileva-Slaveva, Velizar Shivarov, Ihsan Hasan, and Angel Yordanov. "Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer." Medicina 59, no. 4 (2023): 728. http://dx.doi.org/10.3390/medicina59040728.

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Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular im

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Zhang, Xinke, Suijing Wang, Run-Cong Nie, et al. "Immune Microenvironment Characteristics of Urachal Carcinoma and Its Implications for Prognosis and Immunotherapy." Cancers 14, no. 3 (2022): 615. http://dx.doi.org/10.3390/cancers14030615.

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Urachal carcinoma (UrC) is an exceedingly rare tumor and lacks effective treatment. Herein, we characterized an immune microenvironment characteristic of UrC in detail and identified its implications for prognosis and immunotherapy. In total, 37 resections of UrC were stained for CD20, CD3, CD4, CD8, FOXP3, CD68, HLA-DR, CD163, PD1, and PD-L1, as well as mismatch repair protein including MSH2, MSH6, MLH1, and PMS2 by immunohistochemistry. Intratumoral and peritumoral immune cell densities or the proportion of PD1 and PD-L1 expression alongside MSH2, MSH6, MLH1, and PMS2 status were manually ev

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Nath, Karthik, Soi-Cheng Law, Muhammed B. Sabdia, et al. "Intratumoral T cells have a differential impact on FDG-PET parameters in follicular lymphoma." Blood Advances 5, no. 12 (2021): 2644–49. http://dx.doi.org/10.1182/bloodadvances.2020004051.

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Data on the prognostic impact of pretherapy 18F-fluorodeoxyglucose–positron emission tomography (FDG-PET) in follicular lymphoma (FL) is conflicting. The predictive utility of pretherapy total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) on outcome appears to vary between regimens. Chemoimmunotherapies vary in the extent of T-cell depletion they induce. The role of intratumoral T cells on pretherapy FDG-PET parameters is undefined. We assessed pretherapy FDG-PET parameters and quantified intratumoral T cells by multiple methodologies. Low intratumoral T cells as

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Sznurkowski, Jacek Jan, Anton Żawrocki, Janusz Emerich, and Wojciech Biernat. "Prognostic Significance of CD4+and CD8+T Cell Infiltration Within Cancer Cell Nests in Vulvar Squamous Cell Carcinoma." International Journal of Gynecologic Cancer 21, no. 4 (2011): 717–21. http://dx.doi.org/10.1097/igc.0b013e3182131f36.

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Background:The clinicopathological significance of the local spontaneous immune reaction in vulvar squamous cell carcinoma remains unclear. The purpose of this study was to clarify the role of the subtypes of tumor-infiltrating lymphocytes, both individually and synergistically.Methods:Seventy-six patients with verified histopathological data and complete clinical history were included into the study. We collected 76 paraffin-embedded samples of the primary tumor. The presence of CD4+and CD8+T cells was evaluated by immunohistochemistry and compared with commonly recognized prognostic factors.

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Nattamai, Durgha, and Sattva S. Neelapu. "PD-1 Expression Is Markedly Upregulated on Intratumoral CD4+ and CD8+ T Cells in Follicular Lymphoma and Is Associated with T-Cell Exhaustion." Blood 110, no. 11 (2007): 2749. http://dx.doi.org/10.1182/blood.v110.11.2749.2749.

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Abstract Follicular lymphoma is one of the most immune-responsive of all human malignancies. However, immunoregulatory mechanisms in the tumor microenvironment may impair the efficacy of immunotherapies such as vaccines and adoptive T-cell therapy. The inhibitory receptor programmed death 1 (PD1), a negative regulator of activated T cells was recently shown to be upregulated on the surface of HIV-specific CD4+ and CD8+ T cells in humans and was associated with impaired T-cell function. Blockade of the immunoregulatory PD-1/PD-ligand 1 (PD-L1) pathway with antibodies against the PD-L1 augmented

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Wang, Shu, Jose Campos, Marilena Gallotta, et al. "Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+T cells." Proceedings of the National Academy of Sciences 113, no. 46 (2016): E7240—E7249. http://dx.doi.org/10.1073/pnas.1608555113.

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Despite the impressive rates of clinical response to programmed death 1 (PD-1) blockade in multiple cancers, the majority of patients still fail to respond to this therapy. The CT26 tumor in mice showed similar heterogeneity, with most tumors unaffected by anti–PD-1. As in humans, response of CT26 to anti–PD-1 correlated with increased T- and B-cell infiltration and IFN expression. We show that intratumoral injection of a highly interferogenic TLR9 agonist, SD-101, in anti–PD-1 nonresponders led to a complete, durable rejection of essentially all injected tumors and a majority of uninjected, d

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Yang, Zhi-Zhang, Tammy Price-troska, Anne J. Novak, and Stephen M. Ansell. "The Exhausted Intratumoral T Cell Population in B-Cell Non-Hodgkin Lymphoma Is Defined By LAG-3, PD-1 andtim-3 Expression." Blood 126, no. 23 (2015): 2661. http://dx.doi.org/10.1182/blood.v126.23.2661.2661.

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Abstract T-cell exhaustion plays an important role in attenuating the function of immune cells in B-cell non-Hodgkin's lymphoma (NHL) and PD-1 expression is typically used to identify exhausted T-cells. We have however previously shown that not all PD-1+ cells are exhausted and that PD-1 is differentially expressed on two distinct T-cell subpopulations, with high expression on T follicular helper cells and dim expression on exhausted T cells. Other markers are therefore needed to more clearly identify exhausted intratumoral T cells. To further define exhaustion of intratumoral T cells, we dete

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Liu, Zhaopei, Quan Zhou, Zewei Wang, et al. "Intratumoral TIGIT+ CD8+ T-cell infiltration determines poor prognosis and immune evasion in patients with muscle-invasive bladder cancer." Journal for ImmunoTherapy of Cancer 8, no. 2 (2020): e000978. http://dx.doi.org/10.1136/jitc-2020-000978.

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BackgroundT-cell immunoglobulin and ITIM domain (TIGIT) is identified as a novel checkpoint receptor that can facilitate immune escape via mediating T-cell exhaustion in tumors. However, the clinical significance and immune contexture correlation of intratumoral TIGIT+ CD8+ T-cells remain to be further explored in muscle-invasive bladder cancer (MIBC).Methods259 patients with MIBC from two clinical centers (Zhongshan Hospital, n=141; Shanghai Cancer Center, n=118) were analyzed to evaluate the prognostic value and immune contexture association of TIGIT+ CD8+ T-cells through immunohistochemistr

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Yang, Zhi-Zhang, Deanna M. Grote, Steven C. Ziesmer, and Stephen M. Ansell. "PD-1 Expression Defines Two Distinct T-Cell Subpopulations That Differentially Impact Patient Outcomes In Follicular Lymphoma." Blood 122, no. 21 (2013): 366. http://dx.doi.org/10.1182/blood.v122.21.366.366.

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Abstract Background The role of intratumoral PD-1+ T cells and their contribution to patient outcome in follicular lymphoma (FL) has been controversial. While some studies have found that increased numbers of PD-1+ T cells correlate with an inferior prognosis or have no impact on patient outcomes, other studies observed that the numbers of intratumoral PD-1+ T cells are an indicator of a favorable outcome in FL. In previous work, we observed that PD-1 can be expressed by different subsets of intratumoral T cells in FL including T follicular helper (TFH) cells and exhausted T effector cells. Ho

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Dimitrova, Polina D., Savelina L. Popovska, and Ivan N. Ivanov. "A Study on Tumor-Infiltrating Lymphocytes in Different Subtypes of Breast Cancer." Journal of Biomedical and Clinical Research 14, no. 1 (2021): 70–81. http://dx.doi.org/10.2478/jbcr-2021-0008.

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Summary The study aimed to investigate immune cell infiltration in different subtypes of breast cancer (BC). Retrospectively were selected 100 patients with primary BC, grouped into four molecular surrogate subtypes (Luminal A and Luminal B-like, HER2-positive and triple-negative - TN), determined by immunohistochemistry (IHC). In each patient, a percentage of stromal tumor-infiltrating lymphocytes (TILs) was determined by hematoxylin-eosin staining. IHC was performed using primary antibodies CD3, CD4, CD8, CD20, and FOXP3. Immunophenotyped lymphocytes were counted (separately intratumoral and

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Zhang, Yan, Jiayan Gao, Yan He, et al. "Vascular Normalization Was Associated with Colorectal Tumor Regression upon Anti-PD-L1 Combinational Therapy." Journal of Immunology Research 2023 (March 17, 2023): 1–13. http://dx.doi.org/10.1155/2023/5867047.

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Anti-PD-L1 therapy exhibits durable efficacy, but only in a small fraction of cancer patients. The immunosuppressive tumor microenvironment (TME) is a crucial obstacle that impedes cancer immunotherapy. Here, we found that anti-PD-L1 therapy coupled with CD4+ T cell depletion induced colorectal tumor regression and vascular normalization, while monotherapy only retarded tumor growth without affecting the tumor vasculature. Moreover, simultaneous PD-L1 blockade and CD4+ T cell depletion eradicated intratumoral PD-L1+ lymphoid and myeloid cell populations, while additively elevating the proporti

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Yu, Yizhi, Xiaoling Luo, Shuxun Liu, Yuan Xie, and Xuetao Cao. "Intratumoral Expression of MIP-1b Induces Antitumor Responses in a Pre-Established Tumor Model through Chemoattracting T Cells and NK Cells." Blood 104, no. 11 (2004): 5268. http://dx.doi.org/10.1182/blood.v104.11.5268.5268.

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Abstract Direct intratumoral introduction of therapeutic or regulatory genes is a developing technology with potential application for cancer gene therapy. Macrophage inflammatory protein-1 beta (MIP-1b) is a chemokine which can chemoattract immune cells such as T cells. In the present study, murine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus (AdhMIP-1b) carrying the human MIP-1b gene. 24h post-transfection, hMIP-1b levels reached approximately 980 pg/ml in supernatants of 106 hMIP-1b-transfected CT26 cells. Moreover, the supernatants exhibited chemotact

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Markus, Lauren, Lu Sun, Willy Hugo, Annick D. Van den Abbeele, Patrick Wen, and Robert Prins. "IMMU-38. INTRATUMORAL CORRELATION OF MULTIPLEX IMMUNOFLUORESCENCE AND89ZR-CREFMIRLIMAB BERDOXAM IMMUNOPET IN RECURRENT GBM PATIENTS TREATED WITH NEOADJUVANT ANTI-PD-1 +/- ANTI-CTLA-4 THERAPY." Neuro-Oncology 25, Supplement_5 (2023): v150—v151. http://dx.doi.org/10.1093/neuonc/noad179.0570.

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Abstract Glioblastoma (GBM) is a highly aggressive brain tumor that responds poorly to checkpoint blockade inhibitors (ICIs), such as anti-PD-1. We previously reported that neoadjuvant anti-PD-1 therapy activated and recruited T cells into recurrent GBM (rGBM) tumors, but also increased immune checkpoint interactions between T cells and myeloid cells. To overcome this resistance mechanism, we are currently conducting a phase 1B clinical trial of neoadjuvant anti-PD-1 (Nivolumab, BMS) +/- anti-CTLA-4 (Ipilimumab, BMS) combination therapy for rGBM patients (NCT04606316). To evaluate the systemic

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Köksal, Hakan, Michael Herbst, Nicola Marti, and Maries van den Broek. "Abstract 4991: Radiotherapy-induced immunological and therapeutic response depends on stem-like TCF-1+PD-1+CD8+ T-cells." Cancer Research 84, no. 6_Supplement (2024): 4991. http://dx.doi.org/10.1158/1538-7445.am2024-4991.

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Abstract Radiotherapy is a frequently used treatment for cancer. Recent data, including ours, showed that radiotherapy promotes an inflammatory response in the tumor that supports tumor-specific immunity, and in fact, the efficacy of radiotherapy in pre-clinical models depends on CD8+ T-cells. According to our preliminary data, the response to radiotherapy is independent of de novo recruited CD8+ T-cells, suggesting that radiation drives differentiation and proliferation of preexisting intratumoral CD8+ T-cells. Intratumoral CD8+ T-cells are heterogeneous concerning phenotype and function. Und

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Shi, Lewis Z. "Metabolic vulnerabilities of intratumoral T cells and tumor cells." Science Translational Medicine 12, no. 574 (2020): eabf7739. http://dx.doi.org/10.1126/scitranslmed.abf7739.

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Panigoro, Sonar Soni, Sinta Chaira Maulanisa, Ahmad Kurnia, et al. "Total and Intratumoral CD8+ T Cell Expressions are Correlated with Miller Payne Grading and WHO Clinical Response of Neoadjuvant Chemotherapy." Indonesian Biomedical Journal 15, no. 2 (2023): 171–8. http://dx.doi.org/10.18585/inabj.v15i2.2110.

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BACKGROUND: Chemotherapy has reported to stimulate immune system through direct activation of cluster of differentiation (CD)8+ T cells. Neoadjuvant chemotherapy (NAC) is known to improve the clinical response of locally advanced breast cancer (LABC) patients. However, the immune response-related factor evaluation of NAC in LABC patients has not been routinely performed. Therefore, current study was conducted to evaluate the correlation of NAC-induced CD8+ T cell with chemotherapy response based on Miller Payne grading and World Health Organization (WHO) criteria.METHODS: LABC patients were re

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Zhang, Wu-Hu, Wen-Quan Wang, He-Li Gao, et al. "Tumor-Infiltrating Neutrophils Predict Poor Survival of Non-Functional Pancreatic Neuroendocrine Tumor." Journal of Clinical Endocrinology & Metabolism 105, no. 7 (2020): 2217–28. http://dx.doi.org/10.1210/clinem/dgaa196.

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Abstract Objective This study retrospectively characterized the immune infiltrating profile in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). Methods Tumor tissues from the 109-patient Fudan cohort and a 73-patient external validation set were evaluated by immunohistochemistry for 9 immune cell types: tumor-infiltrating neutrophils (TINs), tumor-associated macrophages (TAMs), CD11c+ dendritic cells, anti-NCR1+ natural killer (NK) cells, CD4+ and CD8+ T cells, CD45RO+ memory T cells, FOXP3+ regulatory T cells (Tregs), and CD20+ B cells. Results TINs were primarily distributed in t

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Rafael, Tynisha S., Alberto Gil-Jimenez, Hielke M. de Vries, et al. "Abstract 2488: The penile cancer tumor microenvironment and immunotherapy response: Results from the PERICLES trial." Cancer Research 84, no. 6_Supplement (2024): 2488. http://dx.doi.org/10.1158/1538-7445.am2024-2488.

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Abstract Introduction: The phase II PERICLES trial investigated the efficacy of atezolizumab (anti-PD-L1) for advanced penile cancer, with or without radiotherapy. As previously published, durable responses (progression-free at 12 months) were observed in 4 out of 32 enrolled patients. Here, we present the final overall survival (OS) results and an analysis of potential biomarkers for immunotherapy response. Methods: Preplanned analysis projected that at 27/32 events, the study would have 80% power (2-sided α=0.05) to assess whether the OS for the entire cohort significantly differed from the

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Tseng, William W., Shruti Malu, Minying Zhang, et al. "Analysis of the Intratumoral Adaptive Immune Response in Well Differentiated and Dedifferentiated Retroperitoneal Liposarcoma." Sarcoma 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/547460.

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Treatment options are limited in well differentiated (WD) and dedifferentiated (DD) retroperitoneal liposarcoma. We sought to study the intratumoral adaptive immune response and explore the potential feasibility of immunotherapy in this disease. Tumor-infiltrating lymphocytes (TILs) were isolated from fresh surgical specimens and analyzed by flow cytometry for surface marker expression. Previously reported immune cell aggregates known as tertiary lymphoid structures (TLS) were further characterized by immunohistochemistry. In all fresh tumors, TILs were found. The majority of TILs were CD4 T c

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Shah, Rushil, Konstantinos Aliazis, Anthos Christofides, Angelique A. Pham, Rinku Pal, and Vassiliki A. Boussiotis. "PD-1 Expression By Dendritic Cells Is a Key Regulator of T-Cell Immunity in Cancer." Blood 142, Supplement 1 (2023): 2538. http://dx.doi.org/10.1182/blood-2023-178180.

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Programmed cell death 1 (PD-1) is an inhibitory receptor expressed on a variety of immune cells and a therapeutic target of checkpoint immunotherapy for cancer patients. PD-1 engagement by PD-L1 or PD-L2 can inhibit activation and expansion of tumor antigen-specific T cells. PD-1 expression in tumor-associated macrophages (TAM) correlates with impaired phagocytosis and antigen presenting function and enhanced immunosuppression. PD-1 is also expressed in dendritic cells (DC) and has been shown to correlate negatively with the outcome of DC-based cancer vaccines. On DC, PD-1 can interact with PD

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Adashek, Michael, Abigail Sy Chan, Johnathan Heath, et al. "Prognostic value of tumor infiltrating lymphocytes in epithelioid malignant pleural mesothelioma." Journal of Clinical Oncology 37, no. 15_suppl (2019): e20064-e20064. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e20064.

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e20064 Background: Malignant Mesothelioma (MM) is an aggressive malignancy with survival of 4-12 mo. without treatment and 10% 5-year survival. The response of patients with MM to immunotherapy has increased interest in the tumor immune microenvironment. The purpose of this study was to determine if tumor infiltrating lymphocytes (TIL) are correlated with survival in epithelioid MM. Methods: Immunohistochemistry was performed on specimens from 27 patients with epithelioid mesothelioma using CD4, CD8, and CD68 antibodies. Infiltrate density was scored (0-3+) by pathologist estimate in intratumo

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Khan, Saad M., Rupen Desai, Andrew Coxon, et al. "Impact of CD4 T cells on intratumoral CD8 T-cell exhaustion and responsiveness to PD-1 blockade therapy in mouse brain tumors." Journal for ImmunoTherapy of Cancer 10, no. 12 (2022): e005293. http://dx.doi.org/10.1136/jitc-2022-005293.

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BackgroundGlioblastoma is a fatal disease despite aggressive multimodal therapy. PD-1 blockade, a therapy that reinvigorates hypofunctional exhausted CD8 T cells (Tex) in many malignancies, has not shown efficacy in glioblastoma. Loss of CD4 T cells can lead to an exhausted CD8 T-cell phenotype, and terminally exhausted CD8 T cells (Texterm) do not respond to PD-1 blockade. GL261 and CT2A are complementary orthotopic models of glioblastoma. GL261 has a functional CD4 T-cell compartment and is responsive to PD-1 blockade; notably, CD4 depletion abrogates this survival benefit. CT2A is composed

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Rolig, Annah S., Daniel C. Rose, Grace Helen McGee, Werner Rubas, Saul Kivimäe, and William L. Redmond. "Combining bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) improves systemic antitumor CD8⁺ T cell cytotoxicity over BEMPEG+RT." Journal for ImmunoTherapy of Cancer 10, no. 4 (2022): e004218. http://dx.doi.org/10.1136/jitc-2021-004218.

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BackgroundTumor cell death caused by radiation therapy (RT) triggers antitumor immunity in part because dying cells release adjuvant factors that amplify and sustain dendritic cell and T cell responses. We previously demonstrated that bempegaldesleukin (BEMPEG: NKTR-214, an immunostimulatory IL-2 cytokine prodrug) significantly enhanced the antitumor efficacy of RT through a T cell-dependent mechanism. Because RT can induce either immunogenic or tolerogenic cell death, depending on various factors (radiation dose, cell cycle phase), we hypothesized that providing a specific immunogenic adjuvan

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Rolig, Annah, Daniel Rose, Grace Helen McGee, Saul Kivimae, Werner Rubas, and William Redmond. "596 Combining Bempegaldesleukin (CD122-preferential IL-2 pathway agonist) and NKTR-262 (TLR7/8 agonist) pairs local innate activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A626. http://dx.doi.org/10.1136/jitc-2021-sitc2021.596.

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BackgroundTumor cell death caused by radiation therapy (RT) can trigger anti-tumor immune responses in part because dying cells release adjuvant factors that amplify and sustain DC and T cell responses. We previously demonstrated that bempegaldesleukin (BEMPEG:NKTR-214, a first-in-class CD122-preferential IL-2 pathway agonist), significantly enhanced the anti-tumor efficacy of RT through a T cell-dependent mechanism. Because RT can induce either immunogenic or tolerogenic cell death, depending on a multitude of factors (radiation dose, cell cycle phase, and tumor microenvironment), we hypothes

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Chon, Hongjae. "Effect of STING agonist on tumor immune microenvironment of non-inflamed lung cancer and efficacy of immune checkpoint blockade." Journal of Clinical Oncology 36, no. 5_suppl (2018): 178. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.178.

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178 Background: Cancer immunotherapy targeting immune checkpoints are now emerging as a promising therapeutic strategy in various tumors. However, the treatment of T cell non-inflamed tumor which lacks intratumoral T cell infiltrates are still major clinical hurdle. Therefore, drugs that target signaling pathways to increase T cell infiltration in non-inflamed tumor microenvironment (TME) should be investigated. In this study, we aimed to explore the therapeutic potential of STING agonist in murine model of non-small cell lung cancer to overcome immunotherapy resistance. Methods: C57BL/6 mice,

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Dai, Siyuan, Han Zeng, Zhaopei Liu, et al. "Intratumoral CXCL13+CD8+T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma." Journal for ImmunoTherapy of Cancer 9, no. 2 (2021): e001823. http://dx.doi.org/10.1136/jitc-2020-001823.

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BackgroundChemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4+T cells (TFH) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by TFH have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8+T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13+CD8+T cells in clear cell renal cell carcinoma (ccRCC).MethodsWe analyzed prognostic value and immune contexture that associated with CXCL13

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Murthy, Pranav, Daniel Weber, Sagar N. Sharma, et al. "Intratumoral T cell clonality and survival in a randomized phase II study of preoperative autophagy inhibition in combination with gemcitabine and nab-paclitaxel treatment in patients with resectable pancreatic cancer." Journal of Clinical Oncology 39, no. 15_suppl (2021): e16001-e16001. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e16001.

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e16001 Background: Autophagy is a cell survival mechanism that is upregulated in pancreatic ductal adenocarcinoma (PDAC). PDAC autophagy results in an altered metabolic phenotype that promotes tumor progression, chemotherapeutic resistance, and immune evasion. Methods: We previously completed a randomized phase II clinical trial of preoperative gemcitabine-nab-paclitaxel with (PGH n = 34) and without (PG, n = 30) autophagy inhibition in patients with resectable and borderline resectable PDAC, which demonstrated increased Evans Grade histopathologic and serum CA 19-9 response with autophagy inh

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Rashidian, Mohammad, Martin W. LaFleur, Vincent L. Verschoor, et al. "Immuno-PET identifies the myeloid compartment as a key contributor to the outcome of the antitumor response under PD-1 blockade." Proceedings of the National Academy of Sciences 116, no. 34 (2019): 16971–80. http://dx.doi.org/10.1073/pnas.1905005116.

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Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using 89Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8+ T cells and CD11b+ myeloid cells in response to anti–PD-1 treatment in the MC38 colorectal mouse adenocarcinoma model. Responding and nonresponding tumors showed consistent differences in the distribution of

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Wang, Binglin, Yi Wang, Xiaofan Sun, et al. "CXCR6 is required for antitumor efficacy of intratumoral CD8+ T cell." Journal for ImmunoTherapy of Cancer 9, no. 8 (2021): e003100. http://dx.doi.org/10.1136/jitc-2021-003100.

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BackgroundIncreasing infiltration of CD8+ T cells within tumor tissue predicts a better prognosis and is essential for response to checkpoint blocking therapy. Furthermore, current clinical protocols use unfractioned T cell populations as the starting point for transduction of chimeric antigen receptors (CARs)-modified T cells, but the optimal T cell subtype of CAR-modified T cells remains unclear. Thus, accurately identifying a group of cytotoxic T lymphocytes with high antitumor efficacy is imperative. Inspired by the theory of yin and yang, we explored a subset of CD8+ T cell in cancer with

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Liu, Yi. "Abstract P2-11-01: Comprehensive spatially resolved single-cell analysis of immunotypes in triple-negative breast cancer revealed the central role of intratumoral MHC class II expressions." Clinical Cancer Research 31, no. 12_Supplement (2025): P2–11–01—P2–11–01. https://doi.org/10.1158/1557-3265.sabcs24-p2-11-01.

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Abstract Background: Several studies demonstrated the central role of preexisting immune responses and outcomes in triple-negative breast cancer (TNBC). Emerging studies described 3 distinct tumor-immune microenvironments, termed immunotypes, based on the amount and locations of tumor-infiltrating lymphocytes (TILs), namely immune inflamed (IN), immune excluded (IE), and immune desert (ID). We previously demonstrated that patients with IE tumors had poor outcomes despite having high sTIL. Here, we further evaluated tumor and immune cell characteristics associated with each immunotype. Methods:

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Yang, Isaac, Seunggu J. Han, Michael E. Sughrue, Tarik Tihan, and Andrew T. Parsa. "Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology." Journal of Neurosurgery 115, no. 3 (2011): 505–11. http://dx.doi.org/10.3171/2011.4.jns101172.

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Object The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma. Methods Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tis

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Kinder, Michelle, Jin Lu, Justine Carl та ін. "Abstract 4861: INCA33890 increases CD8+ T-cell effector function compared with pembrolizumab as assessed by single-cell RNA sequencing in human PD-1xTGFβR2 knock-in mouse model". Cancer Research 85, № 8_Supplement_1 (2025): 4861. https://doi.org/10.1158/1538-7445.am2025-4861.

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Abstract INCA33890, a novel PD-1xTGFβR2 bispecific Biclonics® antibody, is designed to selectively inhibit TGFβR2 on PD-1+ cells, leveraging a higher binding affinity for PD-1 over TGFβR2. In preclinical studies using the MC38 colorectal tumor model in human PD-1xTGFβR2 Knock-in mice, INCA33890 had a superior antitumor efficacy compared with pembrolizumab, anti-TGFβR2 or isotype control. This study aimed to uncover the differential mechanism of tumor regression by applying single-cell TCR sequencing (scTCRseq) coupled with single-cell RNA sequencing (scRNAseq) on T cells derived from treated M

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Medina, Benjamin D., Mengyuan Liu, Gerardo A. Vitiello, et al. "Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity." Journal of Experimental Medicine 216, no. 6 (2019): 1359–76. http://dx.doi.org/10.1084/jem.20180660.

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Gastrointestinal stromal tumor (GIST) is driven by an activating mutation in the KIT proto-oncogene. Using a mouse model of GIST and human specimens, we show that intratumoral murine CD103+CD11b− dendritic cells (DCs) and human CD141+ DCs are associated with CD8+ T cell infiltration and differentiation. In mice, the antitumor effect of the Kit inhibitor imatinib is partially mediated by CD103+CD11b− DCs, and effector CD8+ T cells initially proliferate. However, in both mice and humans, chronic imatinib therapy decreases intratumoral DCs and effector CD8+ T cells. The mechanism in our mouse mod

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Salmon, Avery J., Alexander S. Shavkunov, Qi Miao, et al. "BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy." Cancer Immunology Research 10, no. 5 (2022): 597–611. http://dx.doi.org/10.1158/2326-6066.cir-21-0129.

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Abstract Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti–PD-1 and anti–CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen–specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mi

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Guidoboni, Massimo, Anna Maria Granato, Valentina Ancarani, et al. "Effect of vaccination with autologous tumor-loaded dendritic cells on intratumoral regulatory T cells in metastatic melanoma patients." Journal of Clinical Oncology 31, no. 15_suppl (2013): 3040. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3040.

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3040 Background: Vaccination with dendritic cells (DC) is still a valid experimental option for metastatic melanoma (MM). However, only a few patients experience long-lasting objective responses and the majority of clinical responders afterwards relapse and die. Which mechanisms are actually responsible for this “secondary resistance” to whole tumor antigens-loaded DC vaccines is largely unknown. It has been hypothesized that suppressive immune cell subpopulations, regulatory T cells in particular, may progressively accumulate in tumor tissues thus hampering therapy-induced antitumor immune re

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Groeneveldt, Christianne, Priscilla Kinderman, Jordi J. C. van Stigt Thans, et al. "Preinduced reovirus-specific T-cell immunity enhances the anticancer efficacy of reovirus therapy." Journal for ImmunoTherapy of Cancer 10, no. 7 (2022): e004464. http://dx.doi.org/10.1136/jitc-2021-004464.

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BackgroundMany solid tumors do not respond to immunotherapy due to their immunologically cold tumor microenvironment (TME). We and others found that oncolytic viruses (OVs), including reovirus type 3 Dearing, can enhance the efficacy of immunotherapy by recruiting CD8+ T cells to the TME. A significant part of the incoming CD8+ T cells is directed toward reovirus itself, which may be detrimental to the efficacy of OVs. However, here we aim to exploit these incoming virus-specific T cells as anticancer effector cells.MethodsWe performed an in-depth characterization of the reovirus-induced T-cel

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Brunelli, Matteo, Sara Elena Rebuzzi, Valerio Gaetano Vellone, et al. "Feasibility of multiple immunoexpression assay for immune tumor micrornvironment (I-TME) on matched metastatic and primary renal cell carcinoma (RCC) for patient prognostication and predictiveness to immunotherapy (preliminary analyses of the Meet URO 18 study)." Journal of Clinical Oncology 39, no. 15_suppl (2021): e16545-e16545. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e16545.

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e16545 Background: The Meet-URO 18 study is ongoing to assess the prognostic role of I-TME in advanced RCC patients treated with ≥second line nivolumab divided into two cohorts according to clinical benefit [progression-free survival ≥ 12 and ≤ 3 months]. We primarily assessed the feasibility of multiple antibody testing related to I-TME on matched metastases and primary tumor. Methods: Immunohistochemical analyses were used for the TME assessment of T-lineage (CD3, CD4, CD8), FOXP-3, granulocytes (CD15), macrophage-lineage (CD68), natural killer (NK)-cells (CD56), tumor cells (TCs) (CD56), B-

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Sharma, P., E. Sato, D. Bajorin, et al. "CD8+ tumor-infiltrating lymphocytes as a statistically significant marker of disease recurrence and survival in transitional cell carcinoma patients." Journal of Clinical Oncology 24, no. 18_suppl (2006): 4544. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.4544.

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4544 Background: Superficial transitional cell carcinoma (TCC) is an immune-responsive tumor evidenced by immunotherapy trials with BCG demonstrating improved survival. In contrast, more advanced muscle-invasive TCC is not considered an immunologically active tumor. Yet, host immune functions that may have a clinical impact on the biologic activity of these more invasive tumors have not been systemically evaluated. CD8+ T-cells are responsible for cytotoxicity and potential tumor eradication by interaction with antigen plus human leukocyte antigens (HLA). A clear association between intratumor

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Turbitt, William J., Shannon K. Boi, Justin T. Gibson, Rachael M. Orlandella, and Lyse A. Norian. "Diet-Induced Obesity Impairs Outcomes and Induces Multi-Factorial Deficiencies in Effector T Cell Responses Following Anti-CTLA-4 Combinatorial Immunotherapy in Renal Tumor-Bearing Mice." Cancers 13, no. 10 (2021): 2295. http://dx.doi.org/10.3390/cancers13102295.

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Associations between modifiable factors and the efficacy of cancer immunotherapies remain uncertain. We found previously that diet-induced obesity (DIO) reduces the efficacy of an immunotherapy consisting of adenovirus-encoded TRAIL plus CpG oligonucleotide (AdT/CpG) in mice with renal tumors. To eliminate confounding effects of diet and determine whether outcomes could be improved in DIO mice, we evaluated AdT/CpG combined with anti-CTLA-4 in diet-matched, obese-resistant (OB-RES) versus DIO tumor-bearing mice. Therapy-treated OB-RES mice displayed effective renal tumor control and sustained

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Xiao, Y., H. Li, L. Mao, et al. "CD103+ T and Dendritic Cells Indicate a Favorable Prognosis in Oral Cancer." Journal of Dental Research 98, no. 13 (2019): 1480–87. http://dx.doi.org/10.1177/0022034519882618.

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T cells and dendritic cells (DCs) that are positive for the tissue-resident marker CD103 play a vital role in antitumor immunity. In this study, multiplexed immunohistochemistry was applied to stain CD103 and the T-cell marker CD8 as well as the DC marker CD11c on formalin-fixed, paraffin-embedded oral squamous cell carcinoma (OSCC) tissues. Then, the density of CD103+CD8+ and CD103+CD11c+ tumor-infiltrating lymphocytes (TILs) in the intratumoral and stromal regions was calculated, and the correlation of CD103+CD8+ TIL and CD103+CD11c+ TIL density with OSCC patient prognosis was analyzed. The

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Zhang, Cangang, Lei Lei, Xiaofeng Yang, et al. "Single-cell sequencing reveals antitumor characteristics of intratumoral immune cells in old mice." Journal for ImmunoTherapy of Cancer 9, no. 10 (2021): e002809. http://dx.doi.org/10.1136/jitc-2021-002809.

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BackgroundAging has long been thought to be a major risk factor for various types of cancers. However, accumulating evidence indicates increased resistance of old animals to tumor growth. An in-depth understanding of how old individuals defend against tumor invasion requires further investigations.MethodsWe revealed age-associated alterations in tumor-infiltrating immune cells between young and old mice using single-cell RNA and coupled T cell receptor (TCR) sequencing analysis. Multiple bioinformatics methods were adopted to analyze the characteristics of the transcriptome between two groups.

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Burrack, Adam L., Zoe Schmiechen, Ebony Miller та Ingunn Stromnes. "TNF-α blockade improves immunotherapy efficacy by altering the tumor microenvironment and enhancing tumor-specific T cell function in pancreatic ductal adenocarcinoma". Journal of Immunology 208, № 1_Supplement (2022): 119.10. http://dx.doi.org/10.4049/jimmunol.208.supp.119.10.

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Abstract Pancreatic ductal adenocarcinoma (PDA) is a particularly lethal malignancy with a 5-year survival rate of 9%. A recent phase 1 clinical trial suggests CD40 agonist has antitumor activity in some patients. We developed an orthotopic PDA mouse model to track tumor specific CD8 T cells, identify critical antitumor mechanisms, and determine pathways of immunotherapy resistance. Here, we exploit this model to uncover a novel combination immunotherapy that includes CD40 agonist, PD-L1 blockade and TNF-α neutralization (e.g., 4PT). Interfering with TNF-α significantly improves overall mouse

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