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Deciphering immune predictors of immunotherapy response: A multiomics approach at the pan-cancer level

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机构: [1]Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning 110032, China [2]Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China [3]Institute of Health Sciences, China Medical University, Shenyang, Liaoning 110122, China [4]Department of Physiology and Pharmacology, Karolinska Institutet, 171 65 Solna, Sweden [5]Institute of Environmental Medicine, Karolinska Institutet, 171 65 Solna, Sweden [6]School of Medicine, Yunnan University, Kunming, Yunnan 650091, China [7]Department of Reproductive Medicine, The First People’s Hospital of Yunnan Province, Kunming, Yunnan 650021, China [8]Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China [9]Translational Immunology Institute (TII), SingHealth-Duke NUS Academic Medical Centre, Singapore 169856, Singapore [10]Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China [11]Department of Pathology, Nihon University, Tokyo 102-0074, Japan [12]Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore [13]Institut Gustave Roussy, INSERM U1015, Batiment de Me decine Mole culaire 114 rue Edouard Vaillant, 94800 Villejuif, France [14]Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [15]Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA [16]Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 141 52 Huddinge, Sweden [17]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China [18]Shenzhen Research Institute of Shandong University, Shenzhen, Guangdong 518057, China [19]College of Life and Health Sciences, Northeastern University, Shenyang, Liaoning 110819, China [20]School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510000, China [21]The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
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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.Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

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大类 | 1 区 医学
小类 | 1 区 医学:研究与实验 2 区 细胞生物学
第一作者:
第一作者机构: [1]Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning 110032, China [2]Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China [3]Institute of Health Sciences, China Medical University, Shenyang, Liaoning 110122, China [4]Department of Physiology and Pharmacology, Karolinska Institutet, 171 65 Solna, Sweden
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通讯作者:
通讯机构: [1]Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning 110032, China [2]Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China [3]Institute of Health Sciences, China Medical University, Shenyang, Liaoning 110122, China [4]Department of Physiology and Pharmacology, Karolinska Institutet, 171 65 Solna, Sweden [17]Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China [18]Shenzhen Research Institute of Shandong University, Shenzhen, Guangdong 518057, China [19]College of Life and Health Sciences, Northeastern University, Shenyang, Liaoning 110819, China [20]School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510000, China [21]The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
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