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Circadian tumor infiltration and function of CD8+ T cells dictate a temporal response to immunotherapy

GSE260641 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/05/17 Platform GPL24247
Summary
The quantity and quality of tumor-infiltrating lymphocytes (TILs), particularly CD8+ T cells, are parameters linked to tumor control and response to immunotherapy. Yet, it is unknown whether these parameters are controlled in a circadian manner. Here, we show in murine and human cancers that the phenotype and number of TILs show time-of-day differences, which are driven by rhythmic leukocyte infiltration and depend on the circadian clock machinery. These rhythms can be harnessed therapeutically: chimeric antigen receptor (CAR) T cells or immune checkpoint blockers produce significant antitumor benefits when administered at the optimal time of the day, but have little effect when administered at other times. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in melanoma patients and correlate with response to anti-PD-1 therapy. Our data provide unexpected evidence of circadian dynamics in the tumor microenvironment (TME), and suggest the importance of exploiting them in prospective clinical trials.
Published in
Circadian tumor infiltration and function of CD8(+) T cells dictate immunotherapy efficacy
Wang C, Zeng Q, Gül ZM et al. · Cell 2024 · PMID 38723627 · doi:10.1016/j.cell.2024.04.015
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Also filed as BioProject PRJNA1082390 and SRA study SRP492696. Searching any of these in the dataset finder brings you back here.

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