Community series in personalized immuno-oncology: the impact of age and sex on anti-tumor immune responses: Volume II

This Research Topic is the second volume of the “Personalized Immuno-Oncology: The Impact of Age and Sex on Anti-Tumor Immune Responses” Community Series. Please see Volume I here.Immunotherapy has transformed cancer care, yet the same treatment can induce durable remission in one patient and no benefit, or severe toxicity, in another. Age and sex are among the most consistent host factors behind this variability. Aging is accompanied by immunosenescence, inflammaging, metabolic dysregulation, the accumulation of senescent cells and age-related clonal hematopoiesis, all of which reshape immune surveillance and the tumor microenvironment. Because individuals age at different rates, biological age, captured by geriatric assessment, frailty indices or molecular aging clocks, may reflect immune competence better than chronological age. Sex differences arise from sex hormones and from sex chromosomes, including X-linked genes that escape inactivation and loss of the Y chromosome in tumor and immune cells. Importantly, age and sex interact: menopause, declining androgen levels and endocrine cancer therapies shift immune function across the lifespan. Older and frail patients and women also remain underrepresented in clinical trials, leaving gaps in data on efficacy and side effects.Volume I of this Research Topic gathered clinical, translational and mechanistic evidence that age and sex shape responses to immunotherapy and radiotherapy. Volume II aims to move from association to mechanism and application. Key open questions are which age- and sex-dependent pathways in tumor, stromal and immune cells determine response, resistance and toxicity, how age and sex interact rather than act independently, and how these insights can be translated into stratification tools and interventions. Side effects deserve the same attention as efficacy, as age and sex may affect the frequency and pattern of immune-related and radiation-induced adverse events. Radiotherapy deserves particular attention: it is a potent immune modulator and is widely used in older patients, yet its immunological effects are still rarely analyzed with respect to age or sex. We also encourage preclinical studies including aged animals of both sexes and clinical analyses reporting age- and sex-disaggregated outcomes. By connecting immunology, oncology, radiation biology and geriatric oncology, this Research Topic aims to support immuno-oncology strategies tailored to real-world patient populations.This Research Topic welcomes submissions that explore the multifaceted impact of age and sex on treatment-induced anti-tumor immune responses. We encourage manuscripts from a broad range of disciplines, including immunology, oncology, radiation oncology and radiation biology. Topics of interest include, but are not limited to:• Immunosenescence, inflammaging, metabolic reprogramming and cellular senescence, including senescence induced by radio- or chemotherapy, in anti-tumor immunity• Sex hormone signaling and sex chromosome effects (e.g., X-inactivation escape, loss of Y) in tumor and immune cells• Age- and sex-specific efficacy and toxicity of immunotherapy, radiotherapy and their combinations, including immune-related adverse events• Interactions between age and sex, including menopause, androgen decline and endocrine or hormone therapies• Biological versus chronological age: geriatric assessment, frailty, clonal hematopoiesis and aging clocks as predictors for personalized (radio-)immunotherapy• Radiotherapy-immunotherapy combinations tailored to age- and sex-specific immune profiles, including older and frail patients• Strategies to counteract age- or hormone-related immune suppression, such as senotherapeutics, immune rejuvenation or microbiome-based approaches• Preclinical models incorporating aged animals and both sexesWe welcome original research, comprehensive reviews, and perspective articles that provide insights into personalized therapeutic strategies. Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Lisa Weissmann (née Deloch), Maike Trommer, Michael Rückert Source: https://www.frontiersin.org/research-topics/87411/community-series-in-personalized-immuno-oncology-the-impact-of-age-and-sex-on-anti-tumor-immune-responses-volume-ii