Articles de revues sur le sujet « Type 1 regulatory T (Tr1) cells, Cytotoxicity, Immune regulation, granzyme B »

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1

Zhang, ping, Kate H. Gartlan, Simone A. Minnie, et al. "Type-1 regulatory T cells are critical for curative immunotherapy outcomes." Journal of Immunology 210, no. 1_Supplement (2023): 173.11. http://dx.doi.org/10.4049/jimmunol.210.supp.173.11.

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Abstract IL-10 producing CD4 +type-1 regulatory T cells (Tr1) mediate immune tolerance during chronic infection, autoimmunity, and transplantation. We previously demonstrated that eomesodermin (Eomes) promotes Tr1 cell (Eomes +IL-10 +) development after allogenic bone marrow transplantation (alloBMT). Here we define the differentiation trajectory of Tr1 cells and the functional states therein. Eomes −IL-10 −, Eomes +IL-10 −and Eomes +IL-10 +subsets (defined by mCherry and GFP expression respectively) were FACS sorted after alloBMT and transferred into secondary recipients. Eomes +IL-10 +T cell
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Liu, Jeffrey M., Pauline Chen, Brandon Cieniewicz, Alma-Martina Cepika, Rosa Bacchetta, and Maria Grazia Roncarolo. "Engineered Type-1 Regulatory T Cells as Cellular Therapy for Treatment of Immune Mediated Diseases." Journal of Immunology 204, no. 1_Supplement (2020): 87.17. http://dx.doi.org/10.4049/jimmunol.204.supp.87.17.

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Abstract Type 1 regulatory cells (Tr1) are a promising cellular product for suppression of effector T cells in immune mediated diseases, including graft-versus-host-disease (GvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) (Roncarolo et al. Immunity 2018). We have developed an in vitro protocol to produce Tr1 cells by lentiviral transduction of the human IL10 with a constitutive promoter into human CD4+ T cells (Locafaro et al. Molecular Therapy 2017). These engineered Tr1 cells, called LV-10, acquire a characteristic Tr1 cytokine profile (IL-10 and IFN-g high, IL-4 low
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Sultan, Hussein, and Robert Schreiber. "Abstract A075: Cytotoxic Tr1 CD4+ T cells suppress cancer immunotherapy in an antigen-specific manner." Cancer Immunology Research 13, no. 2_Supplement (2025): A075. https://doi.org/10.1158/2326-6074.io2025-a075.

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Abstract The induction of tumor-specific CD8+ cytolytic T cells (CTL) capable of destroying tumors is the ultimate outcome of cancer immunotherapy. While helper CD4+ T cells are often required to foster the induction of antitumor effector CTLs, CD4+ Foxp3+ regulatory T cells impede CTL induction and, consequently, inhibit anti-tumor immunity. Previous studies suggested that other CD4+ T cell populations might also suppress tumor immunity, but the identity, origins and function of these cells remained poorly defined. Herein, we show that FoxP3-negative type 1 regulatory T cells (Tr1) play a maj
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Gallois, Anne, Emmanuelle Godefroy, Olivier Manches, and Nina Bhardwaj. "Effect of matrix metalloproteinase-2 on CD8+ T cell and NK cell responses." Journal of Clinical Oncology 30, no. 15_suppl (2012): e21081-e21081. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e21081.

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e21081 Background: Matrix metalloproteinase 2 (MMP-2) cleaves many components of the extracellular matrix and is over-expressed in several cancers including melanoma. High levels of MMP-2 expressed by tumors are associated with later tumor stages, increased dissemination and poorer survival/prognosis. We recently identified a pathway whereby MMP-2 functions as a human endogenous “conditioner” that skews CD4+ T cells towards a detrimental/inefficient TH2 phenotype through OX40L expression and inhibition of IL-12p70 production. We unraveled the underlying mechanism: MMP-2 degrades the type I IFN
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Jahrsdoerfer, Bernd, Sue E. Blackwell, Thomas Simmet, and George J. Weiner. "Human B Cell Lines and Primary B Cells Actively Secrete Granzyme B in Response to IL-2 Family Cytokines." Blood 110, no. 11 (2007): 1340. http://dx.doi.org/10.1182/blood.v110.11.1340.1340.

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Abstract It is widely believed that the main function of B cells is antibody secretion, but not cellular cytotoxicity. Recently we found that human B cells activated with interleukin 21 (IL-21) and antibodies to the B cell receptor (BCR) or immunostimulatory oligonucleotides (CpG ODN) develop a phenotype similar to that of cytotoxic T lymphocytes. B cells treated in such a way start to secrete large amounts of granzyme B (GrB) instead of antibodies and, as in the case of B-chronic lymphocytic leukemia (B-CLL), acquire the capability to induce apoptosis in bystander B-CLL cells in a GrB-depende
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Roncarolo, Maria Grazia, Manuela Battaglia, Rosa Bacchetta, Megan Levings, and Silvia Gregori. "T-Cell-Mediated Suppression: From Bench to Bedside." Blood 122, no. 21 (2013): SCI—37—SCI—37. http://dx.doi.org/10.1182/blood.v122.21.sci-37.sci-37.

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Abstract T regulatory cells (Tregs) play a pivotal role in promoting and maintaining tolerance. Several subsets of Tregs have been identified but, to date, the best characterized are the CD4+FOXP3+ Tregs (FOXP3+Tregs), thymic-derived or induced in the periphery, and the CD4+ IL-10-producing T regulatory type 1 (Tr1) cells. In the past decade much effort has been dedicated to develop methods for the in vitro induction and expansion of FOXP3+Tregs and of Tr1 cells for Treg-based cell therapy to promote and restore tolerance in T-cell mediated diseases, and for expanding antigen (Ag)-specific Tre
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Greiner, Jochen, Yoko Ono, Susanne Hofmann, et al. "The Mutated Region of Cytoplasmatic Nucleophosmine 1 (NPM1) Elicits Both CD4+ and CD8+ T Cell Responses." Blood 118, no. 21 (2011): 2569. http://dx.doi.org/10.1182/blood.v118.21.2569.2569.

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Abstract Abstract 2569 Introduction In AML, mutations in the nucleophosmin (NPM1) gene are one of the most frequent molecular alterations and predominantly occur in AML with normal cytogenetics. Patients with NPM1 mutation without FLT3-ITD mutation show a favourable prognosis of their disease. The functional role of mutated NPM1 for the improved clinical outcome is under evaluation. Immune responses might be involved in the clinical outcome of the disease. In this work, we demonstrate both CD4+ and CD8+ T cell responses against the mutated region of NPM1. Methods The entire amino acid sequence
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Bae, Jooeun, Brandon Nguyen, Yu-Tzu Tai, et al. "Function and expression of checkpoint inhibitors and immune agonists on immune cells in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM and tumor-specific T lymphocytes." Journal of Clinical Oncology 35, no. 15_suppl (2017): 11577. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.11577.

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11577 Background: Characterization of expression and function of immune regulatory molecules in tumor microenvironment will provide the framework for developing novel therapeutic strategies. Methods: We evaluated the expression and functional impact of various immuno-regulatory molecules, PD-1, PDL-1, PDL-2, LAG3, TIM3, OX40 and GITR, on the CD138+ tumor cells, myeloid derived suppressor cells (MDSC), and T cell subsets from patients with MGUS, SMM and active MM (newly diagnosed, relapsed, relapsed/refractory), and the myeloma-specific cytotoxic T lymphocytes (CTL) induced with XBP1/CD138/CS1
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Chu, Yaya, Susiyan Jiang, Jian Jiang, et al. "Optimizing Ex-Vivo Expanded NK Cell- Mediated Antibody-Dependent Cellular Cytotoxicity (ADCC) Combined with NKTR-255 in Chronic Lymphocytic Leukemia (CLL), Follicular Lymphoma (FL), and Burkitt Lymphoma (BL)." Blood 136, Supplement 1 (2020): 23–24. http://dx.doi.org/10.1182/blood-2020-139822.

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Background: The CD20 molecule is universally expressed by normal B cells in all stages of development, from the pre-B cell up to the mature plasma cell as well as by most B cell malignancies including CLL, FL and BL (Chu/Cairo, BJH, 2016). Rituximab, a monoclonal chimeric anti-CD20 antibody, has been widely used as a chemoimmunotherapeutic regimen in the frontline therapy for patients with CD20+ BL and diffuse large B-cell lymphoma. The addition of rituximab to the CHOP backbone or to standard FAB/LMB therapy has greatly improved outcomes without significantly increasing toxicity in patients w
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Vogel, Alexander J., Thomas Petro, and Deborah Brown. "Elucidating the contribution of IRF3 to effector and memory cytotoxic T cell responses after influenza virus infection." Journal of Immunology 196, no. 1_Supplement (2016): 129.15. http://dx.doi.org/10.4049/jimmunol.196.supp.129.15.

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Abstract The role of interferon regulatory factor (IRF) 3 in initiating the type I interferon response in innate immune cells has been well studied in the context of viral infection. However, it is less clear what impact IRF3 has in shaping and maintaining adaptive immune responses. Previous reports have demonstrated that when restimulated, both CD4 and CD8 T cells from IRF3 knockout (KO) mice have significantly reduced expression of Granzyme B 30 days after infection or following secondary influenza A virus (IAV) challenge. To determine whether deficiencies in Granzyme B correlate with CTL fu
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Chu, Yaya, Keira Foley, Meijuan Tian, et al. "Optimizing Ex-Vivo Expanded NK Cell- Mediated Cellular Cytotoxicity By Obinutuzumab Combined with NKTR-255 in Burkitt Lymphoma (BL)." Blood 142, Supplement 1 (2023): 2063. http://dx.doi.org/10.1182/blood-2023-181996.

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Background: We have previously reported the success of treating children with Burkitt lymphoma (BL) resulting in a ≥90% long-term EFS utilizing short intensive rituximab containing chemoimmunotherapy (Cairo et al, Blood, 2007; Goldman /Cairo et al, Leukemia, 2012, Goldman /Cairo et al, Br J Haematol., 2014; Goldman /Cairo et al, Leukemia, 2021). However, the prognosis is dismal in children who are refractory or progress after chemoimmunotherapy (Cairo et al Br J Haematol. 2018). The mechanisms associated with this poor prognosis are mainly due to chemoradioimmunotherapy resistance and an immun
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Rutella, Sergio, Jayakumar Vadakekolathu, Amanda F. Cashen, et al. "Adoptively Infused Memory-like Natural Killer Cells Impact Adaptive Immune Responses in Patients with Acute Myeloid Leukemia." Blood 142, Supplement 1 (2023): 4813. http://dx.doi.org/10.1182/blood-2023-184986.

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Natural killer (NK) therapies have been challenging owing to antigen escape, restricted trafficking, and limited tumor infiltration, translating into modest clinical benefit. We have shown that memory-like (ML)-NK cells acquire an in vivo differentiated phenotype distinct from conventional NK cells and are well-tolerated without cytokine release syndrome, GVHD, or neurotoxicity. WU-NK-101 (W-NK) is an allogeneic cytokine-reprogrammed, expanded, cryopreserved ML-NK cell product derived from healthy human peripheral blood mononuclear cells, with scalable manufacturability, that is currently in c
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Cariño-Cortés, Raquel. "Immune response in pregnancy: An evolutionary challenge against external and internal stimuli." Mexican Journal of Medical Research ICSA 11, no. 21 (2023): I—II. http://dx.doi.org/10.29057/mjmr.v11i21.10100.

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Several studies from the 1990s found that adverse effects on the fetal environment, such as poor maternal nutrition, can lead to an increased risk of developing chronic diseases in adulthood. 
 These findings led to the fetal origins of disease hypothesis, commonly known as the Barker hypothesis, which proposes that exposures to insults during critical or sensitive windows of development can permanently reprogram physiological responses, thereby giving rise to metabolic and hormonal diseases and disorders later in life.1,2 
 
 Pregnancy remains one of the most vulnerable periods
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Schwartz-Cornil, Isabelle, Michel Bonneau, Marc Dalod, and Nicolas Bertho. "IMPACT OF LARGE MAMMALS MODELS IN IMMUNOLOGY." Reproduction, Fertility and Development 24, no. 1 (2012): 287. http://dx.doi.org/10.1071/rdv24n1ab250.

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Immune responses that control tolerance to self, tolerance to conceptus during pregnancy, and defense against cancer and pathogens are governed by dendritic cells (DC), that are key immune cell types that integrate environment signals and direct T and B cell immune responses. Different DC subtypes exist in mice that each trigger a specific type of immune response, such as cytotoxicity, antibody production, and regulatory processes. Interestingly in mice, it is possible to target specific DC subtypes with antigenised antibodies and obtain a desired type of immune response. However this conceptu
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Maxwell, Kara N. "Abstract NG02: Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers." Cancer Research 84, no. 7_Supplement (2024): NG02. http://dx.doi.org/10.1158/1538-7445.am2024-ng02.

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Abstract Background: Acquired, somatic TP53 mutations leading to loss of p53 tumor suppressive functions are the most common genomic alteration across many cancer types. Breast cancer (BC) is the most common malignancy in females, and 50-75% of estrogen receptor (ER)-negative BC (with or without HER2 amplification) and 10-15% of ER+ BC acquire TP53 alterations. Pathogenic germline variants (PGVs) in TP53 occur in approximately 1:5000 people and lead to the Li Fraumeni Syndrome (LFS) in which individuals have an up to 90% risk of developing cancer over their lifetimes. The most common cancer in
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Sayitoglu, Ece Canan, Robert Arthur Freeborn, and Maria Grazia Roncarolo. "The Yin and Yang of Type 1 Regulatory T Cells: From Discovery to Clinical Application." Frontiers in Immunology 12 (June 10, 2021). http://dx.doi.org/10.3389/fimmu.2021.693105.

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Regulatory T cells are essential players of peripheral tolerance and suppression of inflammatory immune responses. Type 1 regulatory T (Tr1) cells are FoxP3- regulatory T cells induced in the periphery under tolerogenic conditions. Tr1 cells are identified as LAG3+CD49b+ mature CD4+ T cells that promote peripheral tolerance through secretion of IL-10 and TGF-β in addition to exerting perforin- and granzyme B-mediated cytotoxicity against myeloid cells. After the initial challenges of isolation were overcome by surface marker identification, ex vivo expansion of antigen-specific Tr1 cells in th
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Song, Yun, Ning Wang, Lihua Chen, and Liang Fang. "Tr1 Cells as a Key Regulator for Maintaining Immune Homeostasis in Transplantation." Frontiers in Immunology 12 (April 26, 2021). http://dx.doi.org/10.3389/fimmu.2021.671579.

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The immune system is composed of effectors and regulators. Type 1 regulatory T (Tr1) cells are classified as a distinct subset of T cells, and they secret high levels of IL-10 but lack the expression of the forkhead box P3 (Foxp3). Tr1 cells act as key regulators in the immune network, and play a central role in maintaining immune homeostasis. The regulatory capacity of Tr1 cells depends on many mechanisms, including secretion of suppressive cytokines, cell-cell contacts, cytotoxicity and metabolic regulation. A breakdown of Tr1-cell-mediated tolerance is closely linked with the pathogenesis o
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Sultan, Hussein, Yoshiko Takeuchi, Jeffrey P. Ward, et al. "Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy." Nature, July 24, 2024. http://dx.doi.org/10.1038/s41586-024-07752-y.

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AbstractCD4+ T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses1–5, other CD4+ T cells have recently been implicated in inhibiting this response6,7. Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II
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Papp, Gábor, Krisztina Szabó, Ilona Jámbor, et al. "Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation." Frontiers in Immunology 12 (April 16, 2021). http://dx.doi.org/10.3389/fimmu.2021.639308.

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Age-related changes of the immune system lead to an increased morbidity and mortality due to enhanced vulnerability to infectious diseases and malignancies. Recent studies revealed the important effects of physical activity on immune functions, which may largely depend on the type of exercise, its intensity and duration. However, limited information is available regarding the immunological effects of sport activities in older ages. The aim of our study was to examine the changes in a wide spectrum of lymphocyte subtypes after regular workout among healthy elderly individuals. We enrolled 29 el
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Wu, Xiangni, Pin-I. Chen, Robert L. Whitener, et al. "CD39 delineates chimeric antigen receptor regulatory T cell subsets with distinct cytotoxic & regulatory functions against human islets." Frontiers in Immunology 15 (June 28, 2024). http://dx.doi.org/10.3389/fimmu.2024.1415102.

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Human regulatory T cells (Treg) suppress other immune cells. Their dysfunction contributes to the pathophysiology of autoimmune diseases, including type 1 diabetes (T1D). Infusion of Tregs is being clinically evaluated as a novel way to prevent or treat T1D. Genetic modification of Tregs, most notably through the introduction of a chimeric antigen receptor (CAR) targeting Tregs to pancreatic islets, may improve their efficacy. We evaluated CAR targeting of human Tregs to monocytes, a human β cell line and human islet β cells in vitro. Targeting of HLA-A2-CAR (A2-CAR) bulk Tregs to HLA-A2+ cell
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Kucuksezer, Umut Can, Esin Aktas Cetin, Fehim Esen, et al. "The Role of Natural Killer Cells in Autoimmune Diseases." Frontiers in Immunology 12 (February 25, 2021). http://dx.doi.org/10.3389/fimmu.2021.622306.

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Natural killer (NK) cells, the large granular lymphocytes differentiated from the common lymphoid progenitors, were discovered in early 1970’s. They are members of innate immunity and were initially defined by their strong cytotoxicity against virus-infected cells and by their important effector functions in anti-tumoral immune responses. Nowadays, NK cells are classified among the recently discovered innate lymphoid cell subsets and have capacity to influence both innate and adaptive immune responses. Therefore, they can be considered as innate immune cells that stands between the innate and
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Zhou, Kai-Qian, Yu-Cheng Zhong, Ming-Fang Song, et al. "Distinct immune microenvironment of venous tumor thrombus in hepatocellular carcinoma at single-cell resolution." Hepatology, December 10, 2024. https://doi.org/10.1097/hep.0000000000001182.

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Background & Aims: Portal vein tumor thrombus (PVTT) worsens the prognosis of hepatocellular carcinoma by increasing intrahepatic dissemination and inducing portal vein hypertension. However, the immune characteristics of PVTT remain unclear. Therefore, this study aims to explore the immune microenvironment in PVTT. Approach & Results: Time-of-flight mass cytometry (CyTOF) revealed that macrophages and monocytes were the dominant immune cell type in PVTT, with a higher proportion than in primary tumor (PT) and blood (54.1% vs. 26.3% and 9.1%, p<0.05). The differentially enriched clu
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Das, Juhina, Saurav Bera, Nilanjan Ganguly, et al. "The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study." Frontiers in Immunology 15 (March 22, 2024). http://dx.doi.org/10.3389/fimmu.2024.1325161.

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IntroductionMurine tumor growth restriction by neem leaf glycoprotein (NLGP) was established in various transplanted models of murine sarcoma, melanoma and carcinoma. However, the role of NLGP in the sequential carcinogenic steps has not been explored. Thus, tongue carcinogenesis in Swiss mice was induced by 4-nitroquinoline-1-oxide (4NQO), which has close resemblance to human carcinogenesis process. Interventional role of NLGP in initiation-promotion protocol established during 4NQO mediated tongue carcinogenesis in relation to systemic immune alteration and epithelial-mesenchymal transition
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