Lin et al. developed a longitudinal scRNAseq atlas of 441 ICI-treated tumors from 241 patients across 10 cancer types, and identified 4 conserved TIME states. ICI induced temporal TIME remodeling with early T cell activation, resolution of distinct ISG patterns, and progressive stromal and immune restructuring. During treatment, approximately 40% of tumors transitioned between TIME states, with inflamed or B cell-enriched transitions associated with response and survival, while myeloid-dominant states associated with resistance. A baseline 59-gene transition signature was predictive of ICI response and survival across 1,383 tumors from 19 independent cohorts.
Contributed by Shishir Pant
(1) Lin Z (2) Chandra M (3) Srinivas N (4) Ugurel S (5) Becker JC (6) Aran D
Lin et al. developed a longitudinal scRNAseq atlas of 441 ICI-treated tumors from 241 patients across 10 cancer types, and identified 4 conserved TIME states. ICI induced temporal TIME remodeling with early T cell activation, resolution of distinct ISG patterns, and progressive stromal and immune restructuring. During treatment, approximately 40% of tumors transitioned between TIME states, with inflamed or B cell-enriched transitions associated with response and survival, while myeloid-dominant states associated with resistance. A baseline 59-gene transition signature was predictive of ICI response and survival across 1,383 tumors from 19 independent cohorts.
Contributed by Shishir Pant
ABSTRACT: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet the basis of variable patient responses remains unclear. We assemble a longitudinal single-cell RNA sequencing atlas of 441 samples from 241 patients across ten cancer entities to map treatment-associated remodeling of the tumor immune microenvironment (TIME). With a hierarchical reference-guided deep-phenotyping framework, we define 77 immune and stromal subtypes and resolve four conserved TIME subtypes. Approximately 40% of tumors shift between states during therapy, and the transition is more predictive of outcome than the baseline state. Favorable transitions toward inflamed or B cell-enriched subtype track with improved response and survival, while persistence in or shifts toward myeloid dominance indicate resistance. We derive a 59-gene signature that predicted response and survival for 1,383 baseline tumors across 19 independent cohorts. These findings establish immunotype transitions as a central determinant of ICI efficacy, offering new avenues for response prediction and rational immunotherapy design.
Author Info:
(1) Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel. (2) Translational Skin Cancer Research, German Cancer Consortium (DKTK), Partner Site Essen, Medical
Faculty, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. (3) Translational Skin Cancer Research, German Cancer Consortium (DKTK), Partner Site Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, University Hospital Essen, Essen, Germany. (4) German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, University Hospital Essen, Essen, Germany. (5) Translational Skin Cancer Research, German Cancer Consortium (DKTK), Partner Site Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, University Hospital Essen, Essen, Germany. Electronic address: j.becker@dkfz-heidelberg.de. (6) Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel; The Taub Faculty of Computer Science, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: dviraran@technion.ac.il.
