Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade
Background CD8+ tissue-resident memory T (T RM ) cells, marked by CD103 ( ITGAE ) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy. Methods Here, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)). Results ITGAE was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ T RM cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion. Conclusions Our analyses indeed demonstrate that the presence of CD103+ CD8+ T RM cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response.