Lack of CD8⁺ T cell effector differentiation during priming mediates checkpoint blockade resistance in non-small cell lung cancer.

ABSTRACT: In non–small cell lung cancer (NSCLC), response to immune checkpoint blockade (ICB) is associated with programmed cell death ligand 1 expression that is induced by interferon-γ–producing, tumor-infiltrating CD8⁺ T cells. However, not all tumors with a CD8⁺ T cell infiltrate respond to ICB, and little is known about the mechanisms governing ICB resistance in T cell–infiltrated NSCLC. We used an orthotopic NSCLC mouse model to study ICB-refractory CD8⁺ T cell responses. Single-cell RNA sequencing of the NSCLC mouse tumors revealed that lung cancer–specific tumor-infiltrating CD8⁺ T cells exhibited clonal expansion but lacked expression of genes associated with effector and exhausted T cell responses, indicating that they underwent a differentiation

SUBMITTER: Horton BL 

PROVIDER: S-EPMC10786005 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature