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SHR Neuro Cancer Cardio Lipid Metab Microb

Mukherjee, S; Patiyal, S; Pal, LR; Chang, TG; Biswas, S; Dhruba, SR; Stemmer, A; Singh, A; Yousefi-Rad, A; Chen, TH; Wang, B; Marino, D; Shon, W; Yuan, Y; Faries, M; Hamid, O; Reckamp, K; Waissengrin, B; Ornelas, B; Chu, PY; Boudjadi, S; Ley, L; Akbulut, D; Ahmar, NE; Signoretti, S; Braun, DA; Joo, H; Kim, H; Osipov, A; Figlin, RA; Bar, J; Barshack, I; Day, CP; Sargsyan, K; Apolo, AB; Aldape, K; Yang, MH; Atkins, MB; Ronai, ZA; Hoang, DT; Ruppin, E.
Pan-cancer prediction of tumor immune activation and response to immune checkpoint blockade from tumor transcriptomics and histopathology.
bioRxiv. 2025; Doi: 10.1101/2025.06.27.661875 [OPEN ACCESS]
PubMed PUBMED Central FullText FullText_MUG

 

Authors Med Uni Graz:
Sargsyan Karine
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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 accurately inferred from tumor histopathology slides. Finally, slide-inferred TIME_ACT scores predict ICB response across eight unseen cohorts, achieving a mean AUC of 0.72 and a mean odds ratio of 5.02. These findings establish TIME_ACT as a robust, pan-cancer, and low-cost predictor of ICB response.

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