Onkar et al. characterized the immune infiltrate in a cohort of treatment-naive ER+ invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), and discovered a differential role for macrophages within the IDC and ILC tumor microenvironment. Macrophages, not T cells, were the predominant cell type infiltrating tumors beds. IDCs harbored proinflammatory and antigen-presenting M1-like macrophages, and the interplay between macrophages and T cells was associated with longer disease-free survival in this cohort. On the other hand, ILC harbored functionally distinct and immunosuppressive macrophages.
Contributed by Shishir Pant
ABSTRACT: T cell-centric immunotherapies have shown modest clinical benefit thus far for estrogen receptor-positive (ER(+)) breast cancer. Despite accounting for 70% of all breast cancers, relatively little is known about the immunobiology of ER(+) breast cancer in women with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). To investigate this, we performed phenotypic, transcriptional and functional analyses for a cohort of treatment-naive IDC (n_=_94) and ILC (n_=_87) tumors. We show that macrophages, and not T cells, are the predominant immune cells infiltrating the tumor bed and the most transcriptionally diverse cell subset between IDC and ILC. Analysis of cellular neighborhoods revealed an interplay between macrophages and T cells associated with longer disease-free survival in IDC but not ILC. Our datasets provide a rich resource for further interrogation into immune cell dynamics in ER(+) IDC and ILC and highlight macrophages as a potential target for ER(+) breast cancer.
Author Info: (1) Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Grad
Author Info: (1) Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Graduate Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. (2) Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. (3) Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA. (4) Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. (5) Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. (6) Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA. Joint Carnegie Mellon University-University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, PA, USA. (7) Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA. UPMC Hillman Cancer Center, Pittsburgh, PA, USA. (8) UPMC Hillman Cancer Center, Pittsburgh, PA, USA. NSABP Foundation, Pittsburgh, PA, USA. (9) Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. (10) NSABP Foundation, Pittsburgh, PA, USA. (11) Section of Breast Surgery, Division of Surgical Oncology, Department of Surgery, University of Pittsburgh College of Medicine, Magee Women's Hospital of UPMC, Pittsburgh, PA, USA. Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA. (12) UPMC Hillman Cancer Center, Pittsburgh, PA, USA. NSABP Foundation, Pittsburgh, PA, USA. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. Cancer Biology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. (13) Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA. (14) Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA. Cancer Biology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. (15) Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. (16) Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA. oesterreichs@upmc.edu. Cancer Biology Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. oesterreichs@upmc.edu. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. oesterreichs@upmc.edu. (17) Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. dvignali@pitt.edu. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. dvignali@pitt.edu. Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. dvignali@pitt.edu.
