Lung Cancer-Intrinsic SOX2 Expression Mediates Resistance to Checkpoint Blockade Therapy by Inducing Treg-Dependent CD8+ T-cell Exclusion.

ABSTRACT: Tumor cell-intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting tumor progression and resistance to immunotherapy by excluding immune cell populations from the tumor. Several tumor cell-intrinsic pathways have been reported to modulate myeloid-cell and T-cell infiltration, creating "cold" tumors. However, clinical evidence suggests that excluding cytotoxic T cells from the tumor core also mediates immune evasion. In this study, we find that tumor cell-intrinsic SOX2 signaling in non-small cell lung cancer induces the exclusion of cytotoxic T cells from the tumor core and promotes resistance to checkpoint blockade therapy. Mechanistically, tumor cell-intrinsic SOX2 expression upregulates CCL2 in tumor cells, resulting in increased recruitment of r

SUBMITTER: Torres-Mejia E 

PROVIDER: S-EPMC11964848 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature