The Duffy Antigen Receptor for Chemokines (DARC or ACKR1) gene regulates circulating levels of inflammatory chemokines and major alleles of the gene are associated with a myriad of clinical outcomes. There are two unique isoforms of DARC which are expressed from distinct separate promoters, but little is known about the expression or regulation of these isoforms. Using quantitative RT-PCR and Immunohistochemical studies of lymphoblastic cells from relevant ancestry groups, we recently found that a DARC polymorphism, the Duffy Null (Fy-) allele found almost exclusively in African ancestry groups, is associated with altered regulation of these isoforms. Our data indicates that people of African ancestry who carry the Fy- allele will have an altered expression pattern of DARC isoforms. Thusly, we investigated whether the Fy- allele is associated with distinct recruitment of monocytes to breast tumor epithelia, regulated by DARC modulated chemokines. This may translate into a suite of distinct inflammatory responses correlated with specific chemokine action and may explain the disparate clinical outcomes of breast cancer in this population.
Citation Format: Melissa B. Davis, Michele Monteil, Rupali Hire, Elizabeth W. Howerth. The role of DARC in the immunological tumor microenvironment of breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A63.
- ©2015 American Association for Cancer Research.