Recent advances in immuno-oncology have underscored the critical role of the immune system in fighting cancer. However, emerging evidence reveals that both age and sex significantly influence the immune system and consequently anti-tumor immune responses. Older or frail individuals, for example, may experience immunosenescence, increased oxidative stress, metabolic dysregulation, and inflammaging—factors that collectively impair immune function and might affect the efficacy of immunotherapies. Furthermore, it might be crucial to distinguish between chronological age and biological age, evaluated through metabolic markers and comprehensive geriatric assessments, which better reflects the true physiological reserve and immunocompetence of older patients. Meanwhile, sex-dependent hormonal and genetic influences further modulate immune cell activity and tumor interactions, resulting in differential treatment efficacy and tolerance. Notably, the historic exclusion of elderly/frail patients and women from clinical trials has led to critical data gaps regarding both efficacy and side effects. Moreover, the integration of radiotherapy into immuno-oncology protocols has shown promising synergistic effects by modulating the tumor microenvironment, while advances such as immune checkpoint inhibitors and novel biomarkers provide unprecedented opportunities to refine personalized therapeutic strategies.
The primary aim of this Research Topic is to address the challenge of inter-individual variability in anti-tumor immune responses driven by age and sex. Despite significant progress in immunotherapy, patient outcomes remain inconsistent, stemming not only from inherent biological differences but also from the historical underrepresentation of elderly/frail patients and women in clinical trials. This exclusion has resulted in a lack of critical data on treatment efficacy and side effects for these groups. A central problem is to elucidate how aging-related factors—including alterations in metabolism, the onset of inflammaging, and increased frailty—affect immune surveillance, tumor immunogenicity, and treatment responses. By integrating cutting-edge research from the fields of immunology, oncology, radiotherapy and radiation biology, this Research Topic encourages the exploration of innovative combination therapies to enhance treatment efficacy. Ultimately, by bringing together innovative studies that dissect the complex underlying biological processes, the collection aims to support the development of actionable approaches tailoring immuno-oncology interventions to diverse patient populations for improved clinical outcomes.
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, and radiation biology. Topics of interest include, but are not limited to:
• Mechanisms of immunosenescence, metabolic reprogramming, and inflammaging in age-related immune regulation and frailty.
• Sex-specific differences in immune cell function and tumor microenvironment interactions.
• The impact of these factors on the efficacy and safety of cancer treatments.
• Sex-specific differences and sex as a prognostic factor in oncology treatments, response patterns and possible solutions to overcome disparities.
• Comprehensive approaches using geriatric assessment to distinguish biological from chronological age in evaluating anti-tumor immune responses and treatment outcomes.
• Radiotherapy-immunotherapy combinations tailored to age- and sex-specific immune profiles
• Treatment approaches focusing on overcoming frailty-related or hormonal immune suppression
• Biomarkers and prediction tools reflecting biological age and sex-specific immune traits to guide personalized radioimmunotherapy.
We 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.
Keywords: Immuno-oncology, Immunosenescence, Inflammaging, Radioimmunotherapies, Personalized cancer therapy, Anti-tumor immunity, Age-related immune modulation, Sex-specific differences in tumor immunity, Tumor microenvironment, Metabolic dysregulation
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
