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Tytuł:
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Tumoral PD-1hiCD8+ T cells are partially exhausted and predict favorable outcome in triple-negative breast cancer.
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Autorzy:
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Guo L; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Cao C; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Goswami S; The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Huang X; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Ma L; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Guo Y; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, U.S.A.
Yang B; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Li T; The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Chi Y; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Zhang X; The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
Wu J; Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.; Collaborative Innovation Center for Cancer Medicine, Shanghai 200032, P.R. China.
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Źródło:
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Clinical science (London, England : 1979) [Clin Sci (Lond)] 2020 Apr 17; Vol. 134 (7), pp. 711-726.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society
Original Publication: London, Medical Research Society.
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MeSH Terms:
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Biomarkers, Tumor/*immunology
CD8-Positive T-Lymphocytes/*immunology
Lymphocytes, Tumor-Infiltrating/*immunology
Programmed Cell Death 1 Receptor/*immunology
Triple Negative Breast Neoplasms/*immunology
Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/pathology ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Genes, T-Cell Receptor ; Humans ; Immunologic Memory ; Lymphocytes, Tumor-Infiltrating/metabolism ; Lymphocytes, Tumor-Infiltrating/pathology ; Middle Aged ; Phenotype ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/metabolism ; Prospective Studies ; Risk Factors ; Time Factors ; Transcriptome ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/mortality ; Triple Negative Breast Neoplasms/surgery ; Tumor Microenvironment
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Contributed Indexing:
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Keywords: PD-1; T cell exhaustion; prognosis; triple-negative breast cancer
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Substance Nomenclature:
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0 (Biomarkers, Tumor)
0 (PDCD1 protein, human)
0 (Programmed Cell Death 1 Receptor)
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Entry Date(s):
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Date Created: 20200324 Date Completed: 20200720 Latest Revision: 20200720
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Update Code:
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20240105
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DOI:
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10.1042/CS20191261
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PMID:
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32202617
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Tumor-infiltrating PD-1hi dysfunctional CD8+ T cells have been identified in several tumors but largely unexplored in breast cancer (BC). Here we aimed to extensively explore PD-1hiCD8+ T cells in BC, focusing on the triple-negative BC (TNBC) subtype. Flow cytometry was used to study the phenotypes and functions of CD8+ T-cell subsets in peripheral blood and surgical specimens from treatment-naive BC patients. RNA-seq expression data generated to dissect the molecular features of tumoral PD-1neg, PD-1lo and PD-1hi CD8+ T cells. Further, the associations between tumoral PD-1hi CD8+ T cells and the clinicopathological features of 503 BC patients were explored. Finally, multiplexed immunohistochemistry (mIHC) was performed to evaluate in situ PD-1hiCD8+ T cells on the tissue microarrays (TMAs, n=328) for prognostic assessment and stratification of TNBC patients. PD-1hiCD8+ T cells found readily detectable in tumor tissues but rarely in peripheral blood. These cells shared the phenotypic and molecular features with exhausted and tissue-resident memory T cells (TRM) with a skewed TCR repertoire involvement. Interestingly, PD-1hiCD8+ T cells are in the state of exhaustion characterized by higher T-BET and reduced EOMES expression. PD-1hiCD8+ T cells found preferentially enriched within solid tumors, but predominant stromal infiltration of PD-1hiCD8+ T subset was associated with improved survival in TNBC patients. Taken together, tumoral PD-1hiCD8+ T-cell subpopulation in BC is partially exhausted, and their abundance signifies 'hot' immune status with favorable outcomes. Reinvigorating this population may provide further therapeutic opportunities in TNBC patients.
(© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
