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Article Abstract

The identification of circulating predictors of response to ICB therapy is vital as very few of them meet the demands of the clinic. Herein, by using high-dimensionality mass cytometry, we designed a blood immunomap in metastatic NSCLC individuals who underwent anti-PD-1 treatment. We identified heightened frequencies of CD8PD-L1 T cells in non-responders compared to responders. Notably, imaging mass cytometry data revealed that CD8PD-L1 T cells were enriched in tumor biopsies, pleural infusions, and BAL of early-stage NSCLC individuals, proposing this cells subset as candidate not only for the advanced but also for early disease detection. Transcriptomic analysis unveiled that CD8PD-L1 T cells displayed an exhausted phenotype related to their increased frequencies to non-responders to immunotherapy, and gene signatures correlated with the overall survival of an independent cohort. Overall, our study pinpoints immune-related events which may benefit the quest for detection of predictive biomarkers of immunotherapy responses.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375241PMC
http://dx.doi.org/10.1016/j.isci.2025.112804DOI Listing

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