The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy.

Autor:	Waks AG; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Stover DG; Division of Medical Oncology, Ohio State University College of Medicine, Columbus, Ohio., Guerriero JL; Breast Tumor Immunology Laboratory, Susan F. Smith Center for Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts., Dillon D; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Barry WT; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Gjini E; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Hartl C; Breast Tumor Immunology Laboratory, Susan F. Smith Center for Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts., Lo W; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts., Savoie J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Brock J; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Wesolowski R; Division of Medical Oncology, Ohio State University College of Medicine, Columbus, Ohio., Li Z; Department of Pathology, Ohio State University College of Medicine, Columbus, Ohio., Damicis A; Department of Biostatistics, Ohio State University College of Public Health, Columbus, Ohio., Philips AV; Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Wu Y; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Yang F; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Sullivan A; NanoString Technologies, Seattle, Washington., Danaher P; NanoString Technologies, Seattle, Washington., Brauer HA; NanoString Technologies, Seattle, Washington., Osmani W; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Lipschitz M; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Hoadley KA; University of North Carolina School of Medicine, Chapel Hill, North Carolina., Goldberg M; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts., Perou CM; University of North Carolina School of Medicine, Chapel Hill, North Carolina., Rodig S; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Winer EP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Krop IE; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Mittendorf EA; Breast Tumor Immunology Laboratory, Susan F. Smith Center for Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts., Tolaney SM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. sara_tolaney@dfci.harvard.edu.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Aug 01; Vol. 25 (15), pp. 4644-4655. Date of Electronic Publication: 2019 May 06.
DOI:	10.1158/1078-0432.CCR-19-0173
Abstrakt:	Purpose: Hormone receptor-positive/HER2-negative (HR + /HER2 - ) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR + /HER2 - breast tumors. Experimental Design: HR + /HER2 - breast tumors were analyzed before and after neoadjuvant chemotherapy. sTIL were assessed histologically; CD8 + cells, CD68 + cells, and PD-L1 staining were assessed immunohistochemically; whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed. Results: Ninety-six patients were analyzed from two cohorts ( n = 55, Dana-Farber cohort; n = 41, MD Anderson cohort). sTIL, CD8, and PD-L1 on tumor cells were higher in tumors with basal PAM50 intrinsic subtype. Higher levels of tissue-based lymphocyte (sTIL, CD8, PD-L1) and macrophage (CD68) markers, as well as gene expression markers of lymphocyte or macrophage phenotypes (NanoString or CIBERSORT), correlated with favorable response to neoadjuvant chemotherapy, but not with improved distant metastasis-free survival in these cohorts or a large gene expression dataset ( N = 302). In paired pre-/postchemotherapy samples, sTIL and CD8 + cells were significantly decreased after treatment, whereas expression analyses (NanoString) demonstrated significant increase of multiple myeloid signatures. Single gene expression implicated increased expression of immunosuppressive (M2-like) macrophage-specific genes after chemotherapy. Conclusions: The immune microenvironment of HR + /HER2 - tumors differs according to tumor biology. This cohort of paired pre-/postchemotherapy samples suggests a critical role for immunosuppressive macrophage expansion in residual disease. The role of macrophages in chemoresistance should be explored, and further evaluation of macrophage-targeting therapy is warranted. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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