Littérature scientifique sur le sujet « Immunosenecence »

Abstract As potent suppressors of immune responses to self and foreign antigens, Foxp3+ Treg cells are suspected to be involved in immunosuppression leading to cancer, neurodegeneration and infection. Since aging is associated with increased incidence of these diseases, we compared Treg activity in blood, lymphoid organs and lungs of young (5–6 months) and old (21–22 months) C57BL/6 mice, using flow cytometric detection and characterization of Foxp3+ cells. Both the proportion and absolute number of Treg cells increased with age in secondary lymphoid organs but not in blood and lungs. Whereas numbers of thymic and peripheral naive Treg cells decreased with age, the number and proportion of Treg cells with CD103+ memory/effector phenotype increased in peripheral lymphoid tissues. Moreover, the increased Treg activity had in vivo influence since CD40 and CD86 co-stimulatory molecule expression by lymph node dendritic cells (DCs) was impaired in old mice, but could be restored to levels of young mice by inactivating Treg cells with anti-CD25 mAb. Our findings suggest that immunosenecence involves a cumulative imbalance of Treg cell activity and have profound implication for the understanding of age-associated immune dysfunction. This work was supported by the American Foundation for Aging Research (AFAR) and the Department of Veterans Affairs.

Abstract Background Individuals with health conditions have shown higher rates of influenza-related morbidity and mortality compared to healthy individuals and are often prioritized for influenza vaccination. However, vaccination with egg-derived standard quadrivalent inactivated influenza vaccines (IIV4) has shown to be less effective in adults ≥65 years of age largely due to immunosenecence. Two enhanced vaccines, the MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and a high-dose trivalent inactivated influenza vaccine (HD-IIV3), were developed to provide adults ≥65 years with increased protection. The objective of this study was to determine the relative vaccine effectiveness (rVE) of aIIV3 versus IIV4 and HD-IIV3 in preventing influenza-related medical encounters in high-risk adults ≥65 years. Methods A retrospective cohort study was conducted among adults ≥65 years with ≥1 health condition with a record of receiving either aIIV3, IIV4 or HD-IIV3 in the 2017–18 or 2018–19 influenza seasons. Patient-level electronic medical records linked to pharmacy and medical claims were used to ascertain exposure, outcome and covariate information. The primary outcome was influenza-related medical encounters in primary care and hospital (ICD-10 codes J09*–J11*). Inverse probability of treatment weighting was used to obtain odds ratios (ORs) adjusted for age, sex, race, ethnicity, geographic region, comorbidities and week of vaccination for each health condition. rVE was determined using the formula (1-OR)*100 and reported with 95% confidence intervals (CI). Results Overall, 1,755,420 individuals with ≥1 health condition were included for analysis in the 2017–18 season and 2,055,012 individuals in the 2018–19 season. In both seasons, high-risk subjects who received aIIV3 had statistically significantly greater reduction in influenza-related medical encounters as compared to IIV4 (Table 1). Non-statistically significant estimates preclude definitive conclusions for comparisons with HD-IIV3. Table 1. Adjusted relative vaccine effectiveness (rVE) of aIIV3 versus comparators in high-risk patients in the 2017–2018 and 2018–2019 influenza seasons in the U.S. Conclusion The results of this study support the use of aIIV3 in adults ≥65 years of age at high risk for influenza complications and provides further evidence supporting aIIV3 as an effective public health measure against influenza. Disclosures Lauren Fischer, M.A., Seqirus (Consultant) Dan O'Brien, BA, Seqirus (Consultant) Joseph Vasey, PhD, Seqirus (Consultant) Gregg C. Sylvester, MD, Seqirus (Employee) James A. Mansi, PhD, Seqirus (Employee)

AbstractImmune cells infiltrating the central nervous system (CNS) are involved in the defense against invading microbes as well as in the pathogenesis of neuroinflammatory diseases. In these conditions, the presence of several types of immune and inflammatory cells have been demonstrated. However, some studies have also reported low amounts of immune cells that have been detected in the CNS of healthy individuals, but the cell types present have not been systematically analyzed. To do this, we now used brain samples from The Genotype- Tissue Expression (GTEx) project to analyze the relative abundance of 22 infiltrating leukocyte types using a digital cytometry tool (CIBERSORTx). To characterize cell proportions in different parts of the CNS, samples from 13 different anatomic brain regions were used. The data obtained demonstrated that several leukocyte types were present in the CNS. Six leukocyte types (CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes) were present with a proportion higher than 0.05, i.e. 5%. These six cell types were present in most brain regions with only insignificant variation. A consistent association with age was seen with monocytes, CD8 T cells, and follicular helper T cells. Taken together, these data show that several infiltrating immune cell types are present in the non-diseased CNS tissue and that the proportions of infiltrating cells are affected by age in a manner that is consistent with literature on immunosenecence and inflammaging.

With increasing life expectancy, the unique healthcare needs of the older patient are being better appreciated. To address these growing needs, which differ from those of the average adult patient, otolaryngologists must acquire new knowledge and competencies. This chapter provides a broad overview of geriatric otolaryngology and highlights subspecialty topics where otolaryngologists are called upon to administer care. These include age-related hearing loss, balance disorders, sinonasal disease, voice and swallowing disorders, obstructive sleep apnea and head and neck cancer. Geriatric concerns in each of these specific areas have to be addressed in the broader context of geriatric syndromes in coordination with geriatricians or other geriatric-trained providers to advance an integrated, team-based approach to maintaining or restoring the older patients’ well-being. This review contains 3 figures, 2 tables and 161 references Keywords: Cognitive decline, delirium, frailty, age-related hearing loss, presbystasis, presbylarynx, immunosenecense, presbynasalis, vasomotor rhinitis, chronic sinusitis, age-related oflactory decline, dysphagia, head and neck malignant neoplasms, obstructive sleep apnea, geriatric syndromes and perioperative optimization.

With increasing life expectancy, the unique healthcare needs of the older patient are being better appreciated. To address these growing needs, which differ from those of the average adult patient, otolaryngologists must acquire new knowledge and competencies. This chapter provides a broad overview of geriatric otolaryngology and highlights subspecialty topics where otolaryngologists are called upon to administer care. These include age-related hearing loss, balance disorders, sinonasal disease, voice and swallowing disorders, obstructive sleep apnea and head and neck cancer. Geriatric concerns in each of these specific areas have to be addressed in the broader context of geriatric syndromes in coordination with geriatricians or other geriatric-trained providers to advance an integrated, team-based approach to maintaining or restoring the older patients’ well-being. This review contains 3 figures, 2 tables and 161 references Keywords: Cognitive decline, delirium, frailty, age-related hearing loss, presbystasis, presbylarynx, immunosenecense, presbynasalis, vasomotor rhinitis, chronic sinusitis, age-related oflactory decline, dysphagia, head and neck malignant neoplasms, obstructive sleep apnea, geriatric syndromes and perioperative optimization.

With increasing life expectancy, the unique healthcare needs of the older patient are being better appreciated. To address these growing needs, which differ from those of the average adult patient, otolaryngologists must acquire new knowledge and competencies. This chapter provides a broad overview of geriatric otolaryngology and highlights subspecialty topics where otolaryngologists are called upon to administer care. These include age-related hearing loss, balance disorders, sinonasal disease, voice and swallowing disorders, obstructive sleep apnea and head and neck cancer. Geriatric concerns in each of these specific areas have to be addressed in the broader context of geriatric syndromes in coordination with geriatricians or other geriatric-trained providers to advance an integrated, team-based approach to maintaining or restoring the older patients’ well-being. This review contains 3 figures, 2 tables and 161 references Keywords: Cognitive decline, delirium, frailty, age-related hearing loss, presbystasis, presbylarynx, immunosenecense, presbynasalis, vasomotor rhinitis, chronic sinusitis, age-related oflactory decline, dysphagia, head and neck malignant neoplasms, obstructive sleep apnea, geriatric syndromes and perioperative optimization.

Le cancer est une pathologie souvent associée au vieillissement. Plusieurs phénomènes liés à l’inflammaging (inflammation chronique associée à l'âge) sont des marqueurs de sénescence, tels que l’immunosénescence et l’hématopoïèse clonale. Cette inflammation chronique favorise le développement de nombreuses pathologies, telles que les comorbidités cardiovasculaires, tout en réduisant la capacité de réponse immunitaire avec l'âge. L’immunosénescence se caractérise notamment par la diminution du nombre et de la fréquence des lymphocytes T naïfs dans le sang, en raison de leur conversion en lymphocytes T mémoires suite à une exposition naturelle aux pathogènes, auto-antigènes et néo-antigènes. En parallèle, l’involution thymique liée à l'âge réduit la production de nouveaux lymphocytes T naïfs au cours de la vie. Les infections virales chroniques, telles les virus appartenant à la famille des Herpesviridae comme le CMV, contribuent également à l'augmentation des lymphocytes T mémoires en différenciation terminale et à la sénéscence lymphocytaire. Parallèlement à la sénescence immunitaire, on observe l’émergence, avec l'âge et sous l'influence de divers facteurs, d'une hématopoïèse clonale (CH). Elle repose sur la détection de mutations somatiques dans les cellules hématopoïétiques chez des patients sans maladie hématologique avérée. Ces mutations, identifiées grâce au séquençage de nouvelle génération (NGS) dans le sang périphérique, affectent des gènes associés à des pathologies telles que les leucémies myéloïdes aiguës ou les syndromes myélodysplasiques (comme DNMT3A, TET2,ASXL1). Le vieillissement est un facteur de risque majeur de la CH, avec une prévalence supérieure à 10 % après 70 ans, qui augmente progressivement avec l'âge. La CH est également plus fréquente chez les patients atteints de cancer, sous l'effet des traitements ou de facteurs environnementaux (comme le tabac, la radiothérapie et la chimiothérapie). Cependant, son impact pronostique chez les patients atteints de tumeurs solides reste encore peu connu. D’un point de vue thérapeutique, de nombreux progrès ont été réalisés ces dernières années en oncologie solide avec l’avènement des thérapies ciblées et de l’immunothérapie. L’approche antitumorale de l’immunothérapie repose sur un nouveau paradigme: mobiliser le système immunitaire du patient à des fins thérapeutiques. De nombreuses classes de traitements sont en cours de développement, mais les inhibiteurs des points de contrôle immunitaire restent les plus avancés. Ils sont approuvés dans de nombreuses indications, en monothérapie ou en combinaison. La recherche de biomarqueurs a permis de mieux définir les populations candidates à ces traitements. Plusieurs biomarqueurs prédictifs et pronostiques sont désormais disponibles, principalement liés à la tumeur ou à son micro-environnement. Certains biomarqueurs pourraient également être liés au profil immunitaire du patient. L’objectif de cette thèse est d’analyser l’influence de l’hématopoïèse clonale, de l’immuno- sénescence et de l’inflammaging sur l’efficacité des traitements antitumoraux chez des patients atteints de cancers solides
Cancer is a pathology often associated with aging. Several phenomena related to inflammaging (chronic age-related inflammation) are markers of senescence, such as immunosenescence and clonal hematopoiesis. This chronic inflammation promotes the development of many diseases, such as cardiovascular comorbidities, while reducing the capacity for an efficient immune response with age. Immunosenescence is notably characterized by a decrease in the number and frequency of naïve T lymphocytes in the blood, due to their conversion into memory T lymphocytes following natural exposure to pathogens, autoantigens, and neoantigens. In parallel, thymic involution associated with aging reduces the production of new naïve T lymphocytes throughout life. Chronic viral infections, such as those caused by viruses in the Herpesviridae family, including CMV, also contribute to the increase in terminally differentiated memory T lymphocytes and lymphocyte senescence. Alongside immune senescence, the emergence of clonal hematopoiesis (CH) is observed with aging, influenced by various factors. CH is characterized by the detection of somatic mutations in hematopoietic cells in patients without hematologic disease. These mutations, identified through next-generation sequencing (NGS) in peripheral blood, affect genes associated with conditions such as acute myeloid leukemia or myelodysplastic syndromes (e.g., DNMT3A, TET2, ASXL1). Aging is a major risk factor for CH, with a prevalence of over 10% after the age of 70, and it increases progressively with age. CH is also more frequent in cancer patients, influenced by treatments or environmental factors (such as smoking, radiotherapy, and chemotherapy). However, its prognostic impact in patients with solid tumors remains largely unknown. From a therapeutic perspective, significant progress has been made in solid oncology in recent years with the advent of targeted therapies and immunotherapy. The antitumor approach of immunotherapy is based on a new paradigm: mobilizing the patient’s immune system for therapeutic purposes. Several classes of treatments are under development, with immune checkpoint inhibitors leading the way. These inhibitors are approved in numerous indications, either as monotherapy or in combination. The search for biomarkers has refined the selection of candidate populations. Several predictive and prognostic biomarkers are now available, mainly related to the tumor or its microenvironment. Some biomarkers could also be related to the patient's immune profile. The objective of this thesis is to analyze the impact of clonal hematopoiesis, immunosenescence, and inflammaging on the effectiveness of antitumor treatments in patients with solid cancers