Checkpoint blockade immunotherapy relies on T-bet but not Eomes to induce effector function in tumor-infiltrating CD8+ T cells.

ABSTRACT: Coinhibitory receptor blockade is a promising strategy to boost T-cell immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for advanced mechanistic understanding to improve patient outcomes and uncover clinically relevant biomarkers of treatment efficacy. However, the T-cell-intrinsic signaling pathways engaged during checkpoint blockade treatment are not well defined, particularly for combination approaches. Using a murine model to study how effector CD8(+) T-cell responses to tumors may be enhanced in a tolerizing environment, we identified a critical role for the T-box transcription factor T-bet. Combination blockade of CTLA-4, PD-1, and LA

SUBMITTER: Berrien-Elliott MM 

PROVIDER: S-EPMC4324019 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature