Pan-cancer prediction of tumor immune activation and response to immune checkpoint blockade from tumor transcriptomics and histopathology.

ABSTRACT: Accurately predicting which patients will respond to immune checkpoint blockade (ICB) remains a major challenge. Here, we present TIME_ACT, an unsupervised 66-gene transcriptomic signature of tumor immune activation derived from TCGA melanoma data. First, TIME_ACT scores accurately identify tumors with activated immune microenvironments across cancer types. Analysis of spatial features of the tumor microenvironment revealed that TIME_ACT-high regions exhibit dense lymphocyte infiltration near tumor cells, indicating localized immune activation. Second, in 15 anti-PD1 transcriptomic cohorts spanning six cancer types, TIME_ACT outperforms 22 established signatures and methods, achieving a mean AUC of 0.76 and a clinically meaningful mean odds ratio of 6.11. Thirdly, TIME_ACT scores can be ac

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC12312174 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature