Abstract B67: Regulation of a novel cell surface protein in macrophage activity in tumor microenvironment

Abstract

Inflammatory cells and their mediators are an essential component of the tumor microenvironment. Tumor associated macrophages (TAMs) represent a predominant population of inflammatory cells present in the solid tumor and tumor microenvironment. TAMs are associated with tumor progression and metastasis and the infiltration of TAMs or the enrichment of TAM-associated genes relates to poor prognosis and disease outcome in most human tumor types. However, the stimulus and triggers for the tumor cells-macrophage interaction remain unclear. Autotaxin, an ectoenzyme generates smallest phospholipid, lyophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Autotaxin is also known to play important roles in breast cancer, ovarian cancer and many other cancers. LPA is involved in numerous biological processes encompassing cell growth, cell proliferation, cell migration, cancer and metastasis. LPA exerts its functions on different cell types via its different G-protein coupled receptors (GPCRs). More progress has been made in recent years in dissecting the mechanisms of LPA generation and how it directly acts on its target cells. Recently we have shown that LPA converts monocytes into macrophages both in mice and humans. Here, we show that cancer cells in tumor growth are associated with tumor associated macrophages via a signature paracrine link. Our studies identify an unknown signaling link between tumor cells and macrophages. Furthermore, we have functionally characterized these macrophages and the suppression of this paracrine network leads to decrease in tumor growth and its progression. Our preliminary data also shows that blocking of this paracrine link decreases the secretion of proangiogenic factor such as TGF-b, TNF-a, MMP-9, and VEGF. This study suggests that suppression of this paracrine network can act as a new therapeutic approach to control cancer and metastasis. New insights into the role of LPA in regulating immune responses via cancer cells should be explored in the near future. Citation Format: Rashmi Ray, Vivek Rai. Regulation of a novel cell surface protein in macrophage activity in tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B67.