| HRA007955
(Controlled Access)
|
Recent advancements in cancer immunotherapy have significantly improved patient outcomes, yet responses remain moderate. In a phase II clinical trial OOC 001, NCT04718415 involving 51 cancer patients, we conducted singlecell RNA and TCR or BCR sequencing on tumor and blood samples. Our findings associate poor immunotherapy response with reduced levels of CCR7+ CD4 Naive T cells and CD27 Memory B cells, as well as higher expression of immunosenescence-related genes in T and B cell subsets of non-responders. Importantly, studies using syngeneic mouse models and an Ercc1 aging mouse model, along with ongoing trials COIS 01, NCT05724329, validate that senolytics enhance the therapeutic efficacy of immunotherapy in multiple solid tumors by mitigating tumor immunosenescence. These results underscore the critical role of immunosenescence and its senescent features in the tumor microenvironment on immunotherapy outcomes, suggesting that modulation could enhance cancer immunotherapy efficacy. |
