T-cell Senescence in the Tumor Microenvironment
Lihaoyun Huang, Cangang Zhang, Aimin Jiang, Anqi Lin, Lingxuan Zhu, Weiming Mou, Dongqiang Zeng, Zaoqu Liu, Bufu Tang, Jian Zhang, Quan Cheng, Kai Miao, Ting Wei, Peng Luo
Abstract
T-cell senescence occurs in the tumor microenvironment (TME) and influences cancer outcomes as well as the effectiveness of immunotherapies. The TME triggers this T-cell senescence via multiple pathways, including persistent stimulation with tumor-associated antigens, altered metabolic pathways, and activation of chronic inflammatory responses. Senescent T cells exhibit characteristics such as genomic instability, loss of protein homeostasis, metabolic dysregulation, and epigenetic alterations. Direct cross-talk between senescent T cells and other immune cells further exacerbates the immunosuppressive TME. This immune-tumor cell interaction within the TME contributes to impaired tumor antigen recognition and surveillance by T cells. The presence of senescent T cells is often associated with poor prognosis and reduced efficacy of immunotherapies; thus, targeting the tumor-promoting mechanisms of T-cell senescence may provide novel insights into improving tumor immunotherapy and patient outcomes. This review explores the contributors to tumor-derived T-cell senescence, the link between T-cell senescence and tumor prognosis, and the potential for targeting T-cell senescence to enhance tumor immunotherapy.