Special Issue Information

The host's aging immune system (immunosenescence) and the tumor's immunosuppressive microenvironment represent two sides of the same coin, posing fundamental challenges to cancer immunotherapy. While immunotherapies, particularly immune checkpoint inhibitors (ICIs), have revolutionized oncology, their efficacy is often limited by primary or acquired resistance. Aging, a major risk factor for cancer, profoundly shapes the immune landscape, influencing both tumor development and the response to therapy. This creates a critical, yet underexplored, therapeutic paradigm: can we design combination immunotherapies that simultaneously target tumor-specific mechanisms and counteract age-related immune decline?

This Special Issue posits that the next frontier in cancer treatment lies at the intersection of geroscience and immuno-oncology. We must move beyond a one-size-fits-all approach and develop precision strategies that account for the aged host environment. Key questions we seek to address include: How does immunosenescence in T cells, innate immune cells, and the antigen-presentation machinery dictate responses to existing immunotherapies? Can we rejuvenate the aged immune system to enhance anti-tumor immunity? What are the optimal combinations of ICIs with therapies targeting senescence (senolytics/senomorphics), the senescence-associated secretory phenotype (SASP), or age-related metabolic dysregulation? What are the unique toxicities and efficacy profiles of these combinations in pre-clinical models of aging and in older adult patients?

This Special Issue aims to bridge the gap between basic biology and clinical translation. We invite the submission of Original Research, Reviews, and Perspectives that explore innovative immunotherapy combinations designed to be effective within the context of an aging organism. Our goal is to foster the development of safer, more effective therapeutic strategies that not only combat cancer but also promote healthier aging.

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