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Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma.
Liu, Zhichao; Zhang, Yaru; Ma, Ning; Yang, Yang; Ma, Yunlong; Wang, Feng; Wang, Yan; Wei, Jinzhi; Chen, Hongyan; Tartarone, Alfredo; Velotta, Jeffrey B; Dayyani, Farshid; Gabriel, Emmanuel; Wakefield, Connor J; Kidane, Biniam; Carbonelli, Cristiano; Long, Lingyun; Liu, Zhihua; Su, Jianzhong; Li, Zhigang.
Afiliação
  • Liu Z; Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai 200030, China.
  • Zhang Y; School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou, Zhejiang 325101, China.
  • Ma N; Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai 200030, China.
  • Yang Y; Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai 200030, China.
  • Ma Y; School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
  • Wang F; State Key Laboratory of Oncogenes and Related Genes, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
  • Wang Y; Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China.
  • Wei J; Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
  • Chen H; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • Tartarone A; Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ) 85028, Italy.
  • Velotta JB; Department of Thoracic Surgery, Kaiser Permanente Oakland Medical Center, Kaiser Permanente Northern California, Oakland, CA 94611, USA.
  • Dayyani F; Chao Comprehensive Cancer Center, University of California Irvine, Orange, CA 92868, USA.
  • Gabriel E; Department of Surgery, Division of Surgical Oncology, Mayo Clinic, Jacksonville, FL 32224, USA.
  • Wakefield CJ; Department of Internal Medicine, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA.
  • Kidane B; Section of Thoracic Surgery, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
  • Carbonelli C; Pneumology Unit, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo 71013, Italy.
  • Long L; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: lylong@sinh.ac.cn.
  • Liu Z; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: liuzh@cicams.ac.cn.
  • Su J; School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou, Zhejiang 325101, China. Electronic address: sujz@wmu.edu.cn.
  • Li Z; Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai 200030, China. Electronic address: zhigang.li@shsmu.edu.cn.
Cancer Cell ; 41(11): 1852-1870.e9, 2023 11 13.
Article em En | MEDLINE | ID: mdl-37832554
Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8+ Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8+ T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8+ Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8+ T cell effector functions. Overall, our findings unravel progenitor-like CD8+ Tex-SPRY1 cells' role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Carcinoma de Células Escamosas do Esôfago Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Carcinoma de Células Escamosas do Esôfago Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article