Atypical chemokine receptor 1 (DARC/ACKR1) in breast tumors is associated with survival, circulating chemokines, tumor-infiltrating immune cells, and African ancestry

Brittany D. Jenkins, Rachel N. Martini, Rupali Hire, Andrea Brown, Briana Bennett, I'nasia Brown, Elizabeth W. Howerth, Mary Egan, Jamie Hodgson, Clayton Yates, Rick Kittles, Dhananjay Chitale, Haythem Ali, David Nathanson, Petros Nikolinakos, Lisa Newman, Michele Monteil, Melissa B. Davis

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Tumor-specific immune response is an impor-white Americans, and DARC/ACKR1 tumor expression is tant aspect of disease prognosis and ultimately impacts treat-correlated with proinflammatory chemokines, CCL2/MCP-1 ment decisions for innovative immunotherapies. The atypical (P <0.0001) and anticorrelated with CXCL8/IL8 (P <0.0001). chemokine receptor 1 (ACKR1 or DARC) gene plays a pivotal Sub-Saharan African-specific DARC/ACKR1 alleles likely drive role in immune regulation and harbors several single-these correlations. Relapse-free survival (RFS) and overall nucleotide variants (SNV) that are specific to sub-Saharan survival (OS) were significantly longer in individuals African ancestry. with DARC/ACKR1-high tumors (P <1.0 10 16 and Methods: Using computational The Cancer Genome Atlas P <2.2 10 6 , respectively) across all molecular tumor (TCGA) analysis, case–control clinical cohort Luminex assays, subtypes. and CIBERSORT deconvolution, we identified distinct Conclusions: DARC/AKCR1 regulates immune responses in immune cell profile–associated DARC/ACKR1 tumor expres-tumors, and its expression is associated with sub-Saharan sion and race with increased macrophage subtypes and regu-African-specific alleles. DARC/ACKR1-positive tumors will latory T cells in DARC/ACKR1-high tumors. have a distinct immune response compared with DARC/ Results: In this study, we report the clinical relevance of AKCR1-negative tumors. DARC/ACKR1 tumor expression in breast cancer, in the Impact: This study has high relevance in cancer manage-context of a tumor immune response that may be associated ment, as we introduce a functional regulator of inflammatory with sub-Saharan African ancestry. Briefly, we found that for chemokines that can determine an infiltrating tumor immune infiltrating carcinomas, African Americans have a higher cell landscape that is distinct among patients of African proportion of DARC/ACKR1-negative tumors compared with ancestry.

Original languageEnglish (US)
Pages (from-to)690-700
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number4
DOIs
StatePublished - Apr 2019

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Jenkins, B. D., Martini, R. N., Hire, R., Brown, A., Bennett, B., Brown, I., Howerth, E. W., Egan, M., Hodgson, J., Yates, C., Kittles, R., Chitale, D., Ali, H., Nathanson, D., Nikolinakos, P., Newman, L., Monteil, M., & Davis, M. B. (2019). Atypical chemokine receptor 1 (DARC/ACKR1) in breast tumors is associated with survival, circulating chemokines, tumor-infiltrating immune cells, and African ancestry. Cancer Epidemiology Biomarkers and Prevention, 28(4), 690-700. https://doi.org/10.1158/1055-9965.EPI-18-0955