@article{f41c735a8a644f3894d22112969b55c6,
title = "Macrophages promote circulating tumor cell-mediated local recurrence following radiotherapy in immunosuppressed patients",
abstract = "Although radiotherapy (RT) decreases the incidence of locoregional recurrence in breast cancer, patients with triple-negative breast cancer (TNBC) have increased risk of local recurrence following breast-conserving therapy. The relationship between RT and local recurrence is unknown. Here, we tested the hypothesis that recurrence in some instances is due to the attraction of circulating tumor cells to irradiated tissues. To evaluate the effect of absolute lymphocyte count on local recurrence after RT in patients with TNBC, we analyzed radiation effects on tumor and immune cell recruitment to tissues in an orthotopic breast cancer model. Recurrent patients exhibited a prolonged low absolute lymphocyte count when compared with nonrecurrent patients following RT. Recruitment of tumor cells to irradiated normal tissues was enhanced in the absence of CD8+ T cells. Macrophages (CD11b+F480+) preceded tumor cell infiltration and were recruited to tissues following RT. Tumor cell recruitment was mitigated by inhibiting macrophage infiltration using maraviroc, an FDA-approved CCR5 receptor antagonist. Our work poses the intriguing possibility that excessive macrophage infiltration in the absence of lymphocytes promotes local recurrence after RT. This combination thus defines a high-risk group of patients with TNBC.",
author = "Marjan Rafat and Aguilera, {Todd A.} and Marta Vilalta and Bronsart, {Laura L.} and Soto, {Luis A.} and {Von Eyben}, Rie and Golla, {Meghana A.} and Yasaman Ahrari and Stavros Melemenidis and Anosheh Afghahi and Jenkins, {Melissa J.} and Kurian, {Allison W.} and Horst, {Kathleen C.} and Giaccia, {Amato J.} and Graves, {Edward E.}",
note = "Funding Information: The authors thank Drs. Duaa H. Al-Rawi and Erinn B. Rankin for critical evaluation of the article. We thank Drs. Nitin Raj and Laura D. Attardi for generously providing primary MEFs, Dr. Kerriann Casey for her analysis of potential off-target radiation effects in mice, and Tina Seto for providing data from the Oncoshare Project database. This research was financially supported by the Katherine McCormick Advanced Postdoctoral Fellowship and NIH grant# K99CA201304 (M. Rafat); the Ruth L. Kirschstein National Research Service Award PA-14-015 Grant# T32CA121940 (M. Rafat and T.A. Aguilera); the Susan and Richard Levy Gift Fund; the Suzanne Pride Bryan Fund for Breast Cancer Research; the Breast Cancer Research Foundation; the Regents of the University of California's California Breast Cancer Research Program (16OB-0149 and 19IB-0124); the Stanford University Developmental Research Fund; and the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California. The project was supported by an NIH CTSA award number UL1 RR025744. The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology, and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #1U58 DP000807-01 awarded to the Public Health Institute. Publisher Copyright: {\textcopyright} 2018 AACR.",
year = "2018",
month = aug,
day = "1",
doi = "10.1158/0008-5472.CAN-17-3623",
language = "English (US)",
volume = "78",
pages = "4241--4252",
journal = "Cancer research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "15",
}