Deciphering immune predictors of immunotherapy response: A multiomics approach at the pan-cancer level
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<sup>+</sup> and Temra CD8<sup>+</sup> T cells negatively correlate with therapy response, in stark contrast to the positive response associated with CXCL13+ CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Validation with a cohort of 23 colorectal cancer (CRC) samples confirms the significant impact of TGF-β1+ CD4<sup>+</sup> and CXCL13+ CD4<sup>+</sup> and CD8<sup>+</sup> 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.
Authors
- Z. Wang (ORCID: https://orcid.org/0009-0004-2587-9653)
- Chunjie Xiao (ORCID: https://orcid.org/0000-0003-1715-9408)
- Weiyuan Li (ORCID: https://orcid.org/0000-0002-8136-1400)
- Bingyang Liu (ORCID: https://orcid.org/0000-0002-4572-4956)
- Florent Ginhoux (ORCID: https://orcid.org/0000-0002-2857-7755)
- Xuexin Li (ORCID: https://orcid.org/0000-0001-5824-9720)
- Marcus Buggert (ORCID: https://orcid.org/0000-0003-0633-1719)
- Ren Sheng (ORCID: https://orcid.org/0000-0002-2293-8986)
- Joseph Loscalzo
- Lu Pan (ORCID: https://orcid.org/0000-0001-7467-6992)
- Valerie Chew (ORCID: https://orcid.org/0000-0002-5617-0936)
- Xuan Zhang (ORCID: https://orcid.org/0000-0002-3853-517X)
- Long Wang (ORCID: https://orcid.org/0000-0002-2733-7370)
- Xiaolu Zhang (ORCID: https://orcid.org/0000-0002-9350-2880)
Institutions
- Nihon University (JP)
- Agency for Science, Technology and Research (SG)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Shandong University (CN)
- Inserm (FR)
- Shanghai Jiao Tong University (CN)
- Yunnan University (CN)
- Kunming Medical University (CN)
- Singapore Immunology Network (SG)
- Institut Gustave Roussy (FR)
- Karolinska Institutet (SE)
- First People's Hospital of Yunnan Province (CN)
- SingHealth Duke-NUS Academic Medical Centre (SG)
- Fourth Affiliated Hospital of China Medical University (CN)
- City University of Hong Kong, Shenzhen Research Institute (CN)
- First Hospital of China Medical University (CN)
- China Medical University (CN)
- Guangzhou Medical University (CN)
- Northeastern University (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-03-06
- DOI
- https://doi.org/10.1016/j.xcrm.2025.101992
- Citations
- 12
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 9.57