Abstract P6-01-11: Distinct recruitment of tumor-associated immune cells correlates with increased pro-malignant chemokines in tumors expressing epithelial atypical chemokine receptor 1 (ACKR1/DARC), indicating a unique tumor microenvironment

Abstract

The breast tumor microenvironment is a complex assortment of cancer and host immune cells that interact to produce a myriad of clinical outcomes for breast cancer (BrCa) patients.Chemokine receptors, such asthe Atypical Chemokine Receptor 1 (ACKR1), play an important role in maintaining the homeostasis of pro-inflammatory chemokines, as well as influencing the migration of host immune cells. ACKR1 has the ability to modify the breast tumor microenvironment in multiple ways, including sequestering chemokine activity and affecting leukocyte migration. The purpose of this study is to characterize the variation in immune cell signaling between ACKR1 positive and negative tumors, and determine any correlation between ACKR1 and CCL2 (MCP-1) and CXCL8 (IL-8) in various BrCa cell types. Primary breast tumor samples were stained using immunohistochemistry for ACKR1, in addition to various immune cells including, T-cells, B-cells, dendritic cells, and macrophages. We determined levels of circulating chemokines using a Luminex assay kit on whole blood lysate. We also tested the localization of ACKR1-associated chemokines and the abundance of ACKR1 using immunofluorescence techniques. Pilot data collected from primary breast tumor tissue suggested that differential expression of ACKR1 from various tumor subtypes leads to the recruitment of a specific subset of host immune cells to the tumor microenvironment. In our cohort, ACKR1 positive tumors tended to recruit B cells and dendritic cells to the site of the tumor, whereas ACKR1 negative cells did not. We also detected a positive correlation between ACKR1 levels in tumor tissue with CCL2 and CXCL8 levels in the circulating blood of our study group. Finally, co-localization of ACKR1 with CCL2 and CXCL8 was observed in cultured mammalian breast cancer cells. Overall, our pilot data suggests that there is differential recruitment of immune cells within the ACKR1 positive and negative BrCa tumor microenvironments, and that circulating CCL2 and CXCL8 concentrations are positively correlated with ACKR1 levels in BrCa cells. Citation Format: Jenkins BD, Martini RN, Hire R, Monteil MA, Davis MB. Distinct recruitment of tumor-associated immune cells correlates with increased pro-malignant chemokines in tumors expressing epithelial atypical chemokine receptor 1 (ACKR1/DARC), indicating a unique tumor microenvironment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-11.