Decoupling the correlation between cytotoxic and exhausted T lymphocyte transcriptomic signatures enhances melanoma immunotherapy response prediction from tumor expression.

ABSTRACT:

Background

Cytotoxic T lymphocytes (CTL) play a crucial role in anti-cancer immunity. Progression of CTL to terminal exhausted T lymphocytes (ETL) that overexpress inhibitory receptors can substantially decrease effector cytokines production and diminish cytolytic activity and terminal exhausted T cell cannot be reprogrammed by ICIs in tumor microenvironment (TME). However, while the activity levels of CTL and ETL are considered important determinants of immune checkpoint inhibitors (ICIs) response, it has been repeatedly observed that their predictive power of the latter is quite limited. Studying this conundrum on a large scale across the TCGA cohort, we find that ETL and CTL activity (estimated based on conventional gene signatures in the bulk tumor expression) is strongly posit

SUBMITTER: Wang B 

PROVIDER: S-EPMC9928024 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature