Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence Following Radiation Therapy in Immunosuppressed Patients

Details

• Alternative Title:
  Cancer Res
• Personal Author:
  Rafat, Marjan ; Aguilera, Todd A. ; Vilalta, Marta ; Bronsart, Laura L. ; Soto, Luis A. ; von Eyben, Rie ; Golla, Meghana A. ; Ahrari, Yasaman ; Melemenidis, Stavros ; Afghahi, Anosheh ; Jenkins, Melissa J. ; Kurian, Allison W. ; Horst, Kathleen C. ; Giaccia, Amato J. ; Graves, Edward E.
• Description:
  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.| This study establishes the importance of macrophages in driving tumor cell recruitment to sites of local radiation therapy and suggests that this mechanism contributes to local recurrence in women with TNBC that are also immunosuppressed.| http://cancerres.aacrjournals.org/content/canres/78/15/4241/F1.large.jpg |.
• Subjects:
  Animals Article Breast Cancer CD8-Positive T-Lymphocytes Cell Line, Tumor Cell Motility And Migration Cell Movement Chemokines Cytokines Female Growth Factors Humans Lymphokines Macrophages Mastectomy Mice Mice, Inbred BALB C Mice, Nude Neoplasm Recurrence, Local Neoplastic Cells, Circulating Normal Tissue Response To Radiation Receptors, CCR5 Retrospective Studies Triple Negative Breast Neoplasms Tumor Microenvironment And Modification

  More +
• Source:
  Cancer Res. 78(15):4241-4252
• Pubmed ID:
  29880480
• Pubmed Central ID:
  PMC6072588
• Document Type:
  Journal Article
• Funding:
  S10 OD018208/OD/NIH HHSUnited States/ ; HHSN261201000035C/CA/NCI NIH HHSUnited States/ ; T32 CA121940/CA/NCI NIH HHSUnited States/ ; R01 CA197136/CA/NCI NIH HHSUnited States/ ; U58 DP000807/DP/NCCDPHP CDC HHSUnited States/ ; HHSN261201000035I/CA/NCI NIH HHSUnited States/ ; UL1 RR025744/RR/NCRR NIH HHSUnited States/ ; HHSN261201000034C/CA/NCI NIH HHSUnited States/ ; HHSN261201000140C/CA/NCI NIH HHSUnited States/ ; K99 CA201304/CA/NCI NIH HHSUnited States/ ; P01 CA067166/CA/NCI NIH HHSUnited States/
• Volume:
  78
• Issue:
  15
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:62049239b92578f16f52f18af1cc4ff3c2eec991b7b0497d70fc6a01aa2a3a86
• Download URL:
  https://stacks.cdc.gov/view/cdc/57805/cdc_57805_DS1.pdf
• File Type:
  [PDF - 1.34 MB ]