Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors

• Published in: Journal for immunotherapy of cancer 2019-10, Vol.7 (1), p.265-265, Article 265
• Main Authors: Zhu, Li, Narloch, Jessica L., Onkar, Sayali, Joy, Marion, Broadwater, Gloria, Luedke, Catherine, Hall, Allison, Kim, Rim, Pogue-Geile, Katherine, Sammons, Sarah, Nayyar, Naema, Chukwueke, Ugonma, Brastianos, Priscilla K., Anders, Carey K., Soloff, Adam C., Vignali, Dario A. A., Tseng, George C., Emens, Leisha A., Lucas, Peter C., Blackwell, Kimberly L., Oesterreich, Steffi, Lee, Adrian V.
• Format: Article
• Language: English
• Subjects: Adult; Analysis; B cells; Basic Tumor Immunology; Biochemistry; Biomarkers, Tumor; Bone Neoplasms - immunology; Bone Neoplasms - secondary; Brain Neoplasms - immunology; Brain Neoplasms - secondary; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Breast tumors; Cancer; Cancer metastasis; Cancer research; CD8-Positive T-Lymphocytes - immunology; Datasets; Datasets as Topic; Dendritic cells; Dendritic Cells - immunology; Diagnosis; Female; Gastrointestinal Neoplasms - immunology; Gastrointestinal Neoplasms - secondary; Gastrointestinal system; Gene expression; Genes; Genetic aspects; Harbors; Humans; Immune system; Immunohistochemistry; Immunophenotyping; Immunotherapy; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; M2 macrophages; Macrophages; Macrophages - immunology; Management; Metastasis; Metastatic breast cancer; Middle Aged; Ovarian Neoplasms - immunology; Ovarian Neoplasms - secondary; Ovaries; RNA; RNA sequencing; RNA-Seq; Short Report; T cells; T-Lymphocytes, Regulatory - immunology; Tumor Escape; Tumor Microenvironment - immunology; Tumors; Women's health; Womens health
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-019-0755-1

The interplay between the immune system and tumor progression is well recognized. However, current human breast cancer immunophenotyping studies are mostly focused on primary tumors with metastatic breast cancer lesions remaining largely understudied. To address this gap, we examined exome-capture RNA sequencing data from 50 primary breast tumors (PBTs) and their patient-matched metastatic tumors (METs) in brain, ovary, bone and gastrointestinal tract. We used gene expression signatures as surrogates for tumor infiltrating lymphocytes (TILs) and compared TIL patterns in PBTs and METs. Enrichment analysis and deconvolution methods both revealed that METs had a significantly lower abundance of total immune cells, including CD8+ T cells, regulatory T cells and dendritic cells. An exception was M2-like macrophages, which were significantly higher in METs across the organ sites examined. Multiplex immunohistochemistry results were consistent with data from the in-silico analysis and showed increased macrophages in METs. We confirmed the finding of a significant reduction in immune cells in brain METs (BRMs) by pathologic assessment of TILs in a set of 49 patient-matched pairs of PBT/BRMs. These findings indicate that METs have an overall lower infiltration of immune cells relative to their matched PBTs, possibly due to immune escape. RNAseq analysis suggests that the relative levels of M2-like macrophages are increased in METs, and their potential role in promoting breast cancer metastasis warrants further study.