Abstract 2794: CD8+ natural regulatory T cells as antitumor immune effectors in carcinomas of breast and lung

CD8+ T cells are cytolytic effectors of adaptive immunity against invading pathogens, and under various pathological conditions including cancer. In syngeneic, immunocompetent murine models of epithelial cancers, including breast and lung cancer, we observed up-regulation in frequencies of a unique CD8+ T cell population, characterized as CD8+CD25-Foxp3+, referred here as CD8+ natural regulatory T cells. This regulatory cell population was present in very high numbers during initial stages of tumor growth. However, a drastic reduction in CD8+ natural regulatory T cells was observed as tumor burden increased, and also with the onset of metastasis to distant sites, including bone in the case of breast cancer. Upon further investigation of these cells, we observed that they are highly cytotoxic towards the cancer cells. Adoptive transfer of these CD8+ natural regulatory cells obtained from mice with minimal tumor burden resulted in significantly reduced tumor growth in the tumor-bearing recipients. There was also an inverse relationship between CD8+ natural regulatory T cells and plasmacytoid dendritic cells (pDC) as tumor burden increased. Additionally, depletion of pDC, either using depletion antibody or by using a transgenic mouse model lacking pDC, showed increased numbers of CD8+ natural regulatory T cells that resulted in decreased tumor burden. Analysis of a possible molecular mechanism on the role of CD8+ natural regulatory T cells as anti-tumor effectors demonstrated that these cells express PD-1. Furthermore, PD-L1, a ligand for PD-1, is expressed by both pDC and cancer cells in vivo. Ongoing experiments are focused on deciphering a possible role of PD-1 and PD-L1 interaction in determining the fate of CD8+ natural regulatory T cells in the presence of pDC and cancer cells through in vitro assays and using transgenic murine models and depletion antibodies for both PD-1 and PD-L1. Collectively, these data suggest a novel anti-tumor immune population that has a potential to be used as immunotherapy for cancer in conjunction with conventional treatments. Citation Format: Anandi Sawant, Carnella Lee, Cara Schafer, Jessy Deshane, Selvarangan Ponnazhagan. CD8+ natural regulatory T cells as antitumor immune effectors in carcinomas of breast and lung. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2794. doi