dendritic cells; ductal carcinoma in situ; immune escape; immuno-oncology; progenitor T cells; regulatory T cells; single-cell transcriptomic atlas
Abstract :
[en] Immune escape during the ductal carcinoma in situ (DCIS)-to-invasive breast cancer (IBC) transition shapes tumor evolution. Through transcriptomic mapping of the immune landscapes of normal breast, DCIS, and IBC from large patient cohorts, we identified T and myeloid cells as the primary distinguishing features between DCIS and IBC. We discovered cycling regulatory T cells (cycTreg) as an orchestrator of immunosuppression in IBC. cycTreg frequency predicts cytotoxic CD8+, TCR diversity, disease-specific survival in IBC, and recurrence in DCIS. In a rat model of breast cancer, we demonstrated that cycTreg act as precursors to mature Treg and are inducible by tumor-localized type 2 dendritic cells. Profiling of tumors subjected to αOX40 and αPD-L1 therapies revealed an IL-33-mediated fibroblast-cycTreg signaling loop, the disruption of which enhances intratumoral antigen-experienced CD8+ effectors and systemic immunosurveillance. Our study defines cycTreg as critical inducers of immune escape and promising immuno-oncology targets in breast cancer.
Disciplines :
Oncology
Author, co-author :
Bui, Triet Minh; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Jimenez, Ernesto Rojas; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Li, Zheqi; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Foidart, Pierre ; Université de Liège - ULiège > Département des sciences cliniques ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Puleo, Julieann; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Yan, Pengze; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Jhaveri, Aashna; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Yang, Lin; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Nishida, Jun; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Seehawer, Marco; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Cai, Xinran; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Parker, Kimberly Ann; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Qin, Xiaodi; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27705, USA
Sumer, Oyku Ece; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Huang, Xiao-Yun; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Patel, Ashka; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
Dillon, Deborah; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA
McDonnell, Charles H; Sutter Institute for Medical Research, Roseville, CA 95661, USA
Rowberry, Ron; Sutter Institute for Medical Research, Roseville, CA 95661, USA
Jhajj, Shinedeep; Sutter Institute for Medical Research, Roseville, CA 95661, USA
Baker, Catherine; Sutter Institute for Medical Research, Roseville, CA 95661, USA
Brown, Daniel D; Institute for Precision Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA
Strand, Siri H; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
Marks, Jeffrey R; Department of Surgery, Duke University School of Medicine, Durham, NC 27708, USA
Colditz, Graham A; Department of Surgery, Washington University School of Medicine, St. Louis, MO 63108, USA
Park, So Yeon; Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Republic of Korea
Lee, Adrian V; Institute for Precision Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA, UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA
Angelo, Michael; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
McAuliffe, Priscilla F; UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA
Bobolis, Kristie; Sutter Institute for Medical Research, Roseville, CA 95661, USA
West, Robert; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
Dranoff, Glenn; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Hwang, E Shelley; Department of Surgery, Duke University School of Medicine, Durham, NC 27708, USA
Cristea, Simona; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Polyak, Kornelia ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kornelia_polyak@dfci.harvard.edu
NIH. NCI - National Institutes of Health. National Cancer Institute NIH - National Institutes of Health BAEF - Belgian American Educational Foundation FWB - Wallonia-Brussels Federation WBI - Wallonie-Bruxelles International BCRF - Breast Cancer Research Foundation
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