Decoupling the correlation between cytotoxic and exhausted T lymphocyte states enhances melanoma immunotherapy response prediction

Autor: Binbin Wang, Kun Wang, Di Wu, Sahil Sahni, Peng Jiang, Eytan Ruppin
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 6, Pp 109926- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109926
Popis: Summary: Cytotoxic T lymphocyte (CTL) and terminal exhausted T lymphocyte (ETL) activities crucially influence immune checkpoint inhibitor (ICI) response. Despite this, the efficacy of ETL and CTL transcriptomic signatures for response prediction remains limited. Investigating this across the TCGA and publicly available single-cell cohorts, we find a strong positive correlation between ETL and CTL expression signatures in most cancers. We hence posited that their limited predictability arises due to their mutually canceling effects on ICI response. Thus, we developed DETACH, a computational method to identify a gene set whose expression pinpoints to a subset of melanoma patients where the CTL and ETL correlation is low. DETACH enhances CTL’s prediction accuracy, outperforming existing signatures. DETACH signature genes activity also demonstrates a positive correlation with lymphocyte infiltration and the prevalence of reactive T cells in the tumor microenvironment (TME), advancing our understanding of the CTL cell state within the TME.
Databáze: Directory of Open Access Journals