Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges

作者：Qianwen Liu, Jingfeng Li, Xiuqiao Sun, Jiayu Lin, Zhengwei Yu, Yue Xiao, Dan Li, Baofa Sun, Haili Bao, Yihao Liu · 发表于：Journal of Hematology & Oncology · 年份：2025 · DOI：10.1186/s13045-025-01735-w · 被引用次数：33 · 研究领域：Immune cells in cancer、Immune Cell Function and Interaction、Neuroinflammation and Neurodegeneration Mechanisms

Immunosenescence, the age-related decline in immune function, profoundly impacts cancer progression and therapeutic outcomes by fostering a tumor-promoting microenvironment and impairing immune surveillance. This review delineates eleven molecular hallmarks of immunosenescence, including genomic instability, telomere attrition, epigenetic dysregulation, mitochondrial dysfunction, and chronic inflammation, which collectively drive immune cell dysfunction and systemic immunosuppression. Aging reshapes the tumor microenvironment (TME) through recruitment of immunosuppressive cells, senescence-associated secretory phenotypes (SASP), and metabolic reprogramming, contributing to therapy resistance and poor prognosis in elderly patients. While immunotherapies such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell immunotherapy (CAR-T) cells show promise, their efficacy in aging populations is limited by T cell exhaustion, myeloid bias, and altered intercellular communication. Emerging strategies-including senolytics, epigenetic modulators (e.g., histone deacetylase (HDAC) inhibitor), and metabolic interventions (e.g., spermidine, nicotinamide mononucleotide (NMN))-highlight potential avenues to rejuvenate aged immunity. Single-cell multi-omics (single cell RNA-seq, single cell ATAC-seq) further unravel immune cell heterogeneity, revealing tissue-specific chromatin accessibility dynamics and novel targets like interleukin-34 (IL-34) for microglia-mediated ne...