학술논문
Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.
Document Type
Academic Journal
Author
Gil Del Alcazar CR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Huh SJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Ekram MB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Trinh A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Liu LL; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Beca F; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Zi X; Department of Biomedical Engineering, Yale University, New Haven, Connecticut.; Second Military Medical University, Shanghai, P.R. China.; Kwak M; Department of Biomedical Engineering, Yale University, New Haven, Connecticut.; Bergholtz H; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Su Y; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Ding L; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Russnes HG; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Richardson AL; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Pathology, Harvard Medical School, Boston, Massachusetts.; Babski K; Sutter Roseville Medical Center, Roseville, California.; Min Hui Kim E; Sutter Roseville Medical Center, Roseville, California.; McDonnell CH 3rd; Sutter Roseville Medical Center, Roseville, California.; Wagner J; Sutter Roseville Medical Center, Roseville, California.; Rowberry R; Sutter Roseville Medical Center, Roseville, California.; Freeman GJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Dillon D; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Pathology, Harvard Medical School, Boston, Massachusetts.; Sorlie T; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Coussens LM; Department of Cell, Developmental & Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.; Garber JE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; Fan R; Department of Biomedical Engineering, Yale University, New Haven, Connecticut.; Bobolis K; Sutter Roseville Medical Center, Roseville, California.; Allred DC; Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.; Jeong J; Department of Surgery, Gangnam Severance Hospital, Yonsei University Medical College, Seoul, Korea.; Park SY; Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.; Michor F; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Polyak K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. kornelia_polyak@dfci.harvard.edu.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.; Department of Medicine, Harvard Medical School, Boston, Massachusetts.; The Broad Institute, Cambridge, Massachusetts.; Harvard Stem Cell Institute, Cambridge, Massachusetts.
Source
Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101561693 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2159-8290 (Electronic) Linking ISSN: 21598274 NLM ISO Abbreviation: Cancer Discov Subsets: MEDLINE
Subject
Language
English
Abstract
To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45 + CD3 + T cells demonstrated a decrease in CD8 + signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB + CD8 + T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2 + breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression. Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR. See related commentary by Speiser and Verdeil, p. 1062 This article is highlighted in the In This Issue feature, p. 1047 .
(©2017 American Association for Cancer Research.)
(©2017 American Association for Cancer Research.)