Senescent T cells within the tumor microenvironment are a potent driver for tumor growth, stemness, and chemotherapy resistance

T cell senescence is an important dysfunctional state associated with tumor progression, but whether senescent T (Tsen) cells directly reprogram tumor cell behavior remains unknown. Here, single-cell transcriptomic analyses identify abundant Tsen cells across breast, colorectal, and lung cancers. Tsen cells actively promote tumor growth, metastasis, stemness, and chemotherapy resistance by reprogramming tumor cells in vitro and in vivo. Mechanistically, lipid-enriched senescence-associated secretory phenotypes (SASPs) from Tsen cells drive metabolic remodeling and activate STAT1/STAT3 signaling in tumor cells, establishing a pro-tumorigenic state. Therapeutically, depletion of Tsen cells or disruption of tumor lipid metabolic reprogramming suppresses Tsen-mediated tumor progression and metastasis in vivo. Our findings establish Tsen cells as active orchestrators of tumor cell biological functions through lipid-rich SASP-dependent intercellular communication and reveal a previously unrecognized mechanism linking immune senescence to cancer progression. Targeting Tsen cells or their metabolic crosstalk with tumor cells can enhance anti-tumor immunity and improve therapeutic responses.