TY - JOUR
T1 - Deciphering immune predictors of immunotherapy response
T2 - A multiomics approach at the pan-cancer level
AU - Li, Xuexin
AU - Pan, Lu
AU - Li, Weiyuan
AU - Liu, Bingyang
AU - Xiao, Chunjie
AU - Chew, Valerie
AU - Zhang, Xuan
AU - Long, Wang
AU - Ginhoux, Florent
AU - Loscalzo, Joseph
AU - Buggert, Marcus
AU - Zhang, Xiaolu
AU - Sheng, Ren
AU - Wang, Zhenning
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/4/15
Y1 - 2025/4/15
N2 - Immune checkpoint blockade (ICB) therapy has transformed cancer treatment, yet many patients fail to respond. Employing single-cell multiomics, we unveil T cell dynamics influencing ICB response across 480 pan-cancer and 27 normal tissue samples. We identify four immunotherapy response-associated T cells (IRATs) linked to responsiveness or resistance and analyze their pseudotemporal patterns, regulatory mechanisms, and T cell receptor clonal expansion profiles specific to each response. Notably, transforming growth factor β1 (TGF-β1)+ CD4+ and Temra CD8+ T cells negatively correlate with therapy response, in stark contrast to the positive response associated with CXCL13+ CD4+ and CD8+ T cells. Validation with a cohort of 23 colorectal cancer (CRC) samples confirms the significant impact of TGF-β1+ CD4+ and CXCL13+ CD4+ and CD8+ T cells on ICB efficacy. Our study highlights the effectiveness of single-cell multiomics in pinpointing immune markers predictive of immunotherapy outcomes, providing an important resource for crafting targeted immunotherapies for successful ICB treatment across cancers.
AB - Immune checkpoint blockade (ICB) therapy has transformed cancer treatment, yet many patients fail to respond. Employing single-cell multiomics, we unveil T cell dynamics influencing ICB response across 480 pan-cancer and 27 normal tissue samples. We identify four immunotherapy response-associated T cells (IRATs) linked to responsiveness or resistance and analyze their pseudotemporal patterns, regulatory mechanisms, and T cell receptor clonal expansion profiles specific to each response. Notably, transforming growth factor β1 (TGF-β1)+ CD4+ and Temra CD8+ T cells negatively correlate with therapy response, in stark contrast to the positive response associated with CXCL13+ CD4+ and CD8+ T cells. Validation with a cohort of 23 colorectal cancer (CRC) samples confirms the significant impact of TGF-β1+ CD4+ and CXCL13+ CD4+ and CD8+ T cells on ICB efficacy. Our study highlights the effectiveness of single-cell multiomics in pinpointing immune markers predictive of immunotherapy outcomes, providing an important resource for crafting targeted immunotherapies for successful ICB treatment across cancers.
KW - immunotherapy
KW - multiomics
KW - pan-cancer
KW - single cell
UR - http://www.scopus.com/inward/record.url?scp=105002431296&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2025.101992
DO - 10.1016/j.xcrm.2025.101992
M3 - Article
C2 - 40054456
AN - SCOPUS:105002431296
SN - 2666-3791
VL - 6
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 4
M1 - 101992
ER -