Association of Fusobacterium nucleatum with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment.
| Autor: | Borowsky J; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Department of Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.; Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia., Haruki K; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Lau MC; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Dias Costa A; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Väyrynen JP; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland., Ugai T; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Arima K; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., da Silva A; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Felt KD; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Zhao M; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Gurjao C; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Twombly TS; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Fujiyoshi K; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Väyrynen SA; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Hamada T; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Mima K; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Bullman S; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington., Harrison TA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington., Phipps AI; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.; Department of Epidemiology, University of Washington, Seattle, Washington., Peters U; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.; Department of Epidemiology, University of Washington, Seattle, Washington., Ng K; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Meyerhardt JA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Song M; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts., Giovannucci EL; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Wu K; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Zhang X; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Freeman GJ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Huttenhower C; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Garrett WS; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Chan AT; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Leggett BA; Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.; The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia., Whitehall VLJ; Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.; Conjoint Internal Medicine Laboratory, Pathology Queensland, Queensland Health, Brisbane, Queensland, Australia., Walker N; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.; Envoi Specialist Pathologists, Brisbane, Queensland, Australia., Brown I; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.; Envoi Specialist Pathologists, Brisbane, Queensland, Australia., Bettington M; Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.; Envoi Specialist Pathologists, Brisbane, Queensland, Australia., Nishihara R; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Fuchs CS; Yale Cancer Center, New Haven, Connecticut.; Department of Medicine, Yale School of Medicine, New Haven, Connecticut.; Smilow Cancer Hospital, New Haven, Connecticut., Lennerz JK; Department of Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Giannakis M; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Nowak JA; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. sogino@bwh.harvard.edu janowak@bwh.harvard.edu., Ogino S; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. sogino@bwh.harvard.edu janowak@bwh.harvard.edu.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, Massachusetts. |
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| Jazyk: | angličtina |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 May 15; Vol. 27 (10), pp. 2816-2826. Date of Electronic Publication: 2021 Feb 25. |
| DOI: | 10.1158/1078-0432.CCR-20-4009 |
| Abstrakt: | Purpose: While evidence indicates that Fusobacterium nucleatum ( F. nucleatum ) may promote colorectal carcinogenesis through its suppressive effect on T-cell-mediated antitumor immunity, the specific T-cell subsets involved remain uncertain. Experimental Design: We measured F. nucleatum DNA within tumor tissue by quantitative PCR on 933 cases (including 128 F. nucleatum -positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on Bifidobacterium , microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages [TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay]. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between F. nucleatum and T-cell subsets. Results: The amount of F. nucleatum was inversely associated with tumor stromal CD3 + lymphocytes [multivariable OR, 0.47; 95% confidence interval (CI), 0.28-0.79, for F. nucleatum -high vs. -negative category; P Conclusions: The amount of tissue F. nucleatum is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells. (©2021 American Association for Cancer Research.) |
| Databáze: | MEDLINE |
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