Blood immunomap for prediction of responses to anti-PD-1 immunotherapy in metastatic non-small cell lung cancer

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 CD8+PD-L1+ T cells in non-responders compared responders. Notably, Imaging Mass Cytometry data revealed that CD8+PD-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 CD8+PD-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. RNA-seq profiling of FACS-sorted human CD8+ T cells based on PD-L1 expression (positive vs. negative).