The duffy antigen receptor for chemokines (DARC) influences levels of tumor-associated leukocytes in the breast tumor microenvironment.
Martini R, Jenkins BD, Yates C, Newman L, and Davis M. The duffy antigen receptor for chemokines (DARC) influences levels of tumor-associated leukocytes in the breast tumor microenvironment. Cancer Immunol Res 2019; 7(2 Suppl).
Cancer Immunol Res
The regulation of immune cell infiltration into the tumor microenvironment can influence disease prognosis. The specific populations that are present can inform potential treatment options. This work investigates immune cell regulation in the breast cancer tumor microenvironment, specifically how an atypical chemokine receptor, known as the Duffy Antigen Receptor for Chemokines (DARC/ACKR1) can influence levels of leukocyte populations in the breast tumor environment. DARC is a nonsignaling receptor able to bind both the CC and CXC classes of chemokines, and mainly functions to modulate levels of chemokines in circulation, and aid in chemokine transport in tissues. In this regard, DARC expression may determine the profile of immune response.To investigate DARC expression and its effects on tumor-associated leukocyte (TAL) populations, we obtained RNAseq data from The Cancer Genome Atlas (TCGA) Breast Cancer cohort. We proceeded through our analysis with those samples denoted as primary tumor samples (n=400). To estimate the relative abundance of TAL populations, we used the CIBERSORT online platform, which estimates fractions of 22 different TAL populations based on gene expression data. After completing the CIBERSORT analysis, we proceeded with only those samples that had a significant CIBERSORT output (n=167). In our analysis, we found that the total abundance of all TALs was significantly higher in tumors that have high DARC expression (p < 0.0001), and that DARC expression and the TAL abundance are positively and significantly correlated (R = 0.545, p < 0.0001). When we investigated specific TAL populations, we saw that B cell, T-cell, monocyte and macrophage populations were significantly increased in tumors with high DARC expression.