Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade.

ABSTRACT:

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.

SUBMITTER: Banchereau R 

PROVIDER: S-EPMC8032254 | biostudies-literature |

REPOSITORIES: biostudies-literature