Immunosenescence in prostate cancer: from aging-related immune dysfunction to therapeutic opportunities

Juntao Guo, Ke Wu, Zheng M, Guo S, Fang Wang, Lingxiang Lu

Prostate cancer is a typical age-associated malignancy, and increasing evidence suggests that age-related immune alterations play an important role in its initiation, progression, and therapeutic response. Immunosenescence, characterized by impaired immune surveillance, reduced effector-cell function, contraction of the naïve T-cell repertoire, and persistent low-grade inflammation, may contribute to the establishment of a tumor-permissive microenvironment in older patients. In prostate cancer, these changes are particularly relevant because the disease often develops in an immunologically “cold” and suppressive tumor milieu. In addition to systemic immune aging, cellular senescence and the senescence-associated secretory phenotype (SASP) further reshape the local microenvironment by promoting chronic inflammation, stromal remodeling, and immune dysfunction. Together, immunosenescence, inflammaging, and senescence-related signaling may facilitate tumor persistence, immune escape, and resistance to therapy. Emerging therapeutic strategies therefore extend beyond tumor-intrinsic targets and include optimization of immunotherapy, reprogramming of the tumor microenvironment, and targeting of senescent cells or SASP-related pathways. A deeper understanding of how aging-related immune dysfunction interacts with prostate cancer biology may help improve patient stratification and support the development of more individualized treatment strategies for older prostate cancer patients.