biostudies-literatureLiu JNatural Science Foundation of Jiangxi ProvinceNational Natural Science Foundation of China131https://www.ebi.ac.uk/biostudies/studies/S-EPMC12274262biostudies-literatureUnknown38(5)Functional exhaustion of T lymphocytes is considered an important factor in the failure of tumor treatment. Accumulating evidence has shown that tumor cells cultivate their immune microenvironment through secreting exosomes. However, the mechanism through which tumor cell-derived exosomes participate in the regulation of lymphocyte function remains unclear. In this study, we found that exosomes derived from prostate cancer (PCa) cells were able to upregulate the expression of PD-1 and TIM-3 in CD8⁺ T cells, inducing the secretion of cytokines related to T cell exhaustion and significantly decreasing the ability to kill PCa cells. Importantly, our data indicated that treatment with GW4869 could reverse the effects of PCa-derived exosomes on CD8⁺ T cells and further inhHuman cellBlocking secretion of exosomes by GW4869 dampens CD8<sup>+</sup> T cell exhaustion and prostate cancer progression.PMC122742628236050820224BAB206059Liu JYuan FHu YHuang YWang RGuo HLiu SRong JWang ZfalseBlocking secretion of exosomes by GW4869 dampens CD8<sup>+</sup> T cell exhaustion and prostate cancer progression.Functional exhaustion of T lymphocytes is considered an important factor in the failure of tumor treatment. Accumulating evidence has shown that tumor cells cultivate their immune microenvironment through secreting exosomes. However, the mechanism through which tumor cell-derived exosomes participate in the regulation of lymphocyte function remains unclear. In this study, we found that exosomes derived from prostate cancer (PCa) cells were able to upregulate the expression of PD-1 and TIM-3 in CD8⁺ T cells, inducing the secretion of cytokines related to T cell exhaustion and significantly decreasing the ability to kill PCa cells. Importantly, our data indicated that treatment with GW4869 could reverse the effects of PCa-derived exosomes on CD8⁺ T cells and further inh2025-01-01T00:00:00Z2025 Jul2026-03-16T07:19:13.292Z2025-08-17T03:05:35.028ZS-EPMC122742624068195110.1007/s13577-025-01257-0