Lysophosphatidic Acid Inhibits CD8 T-cell Activation and Control of Tumor Progression

• DOI: 10.1158/2326-6066.cir-13-0043-t
• Publication Date: 2013-08-06T04:44:13Z
• Authors: Shannon K. Oda; Pamela Strauch; Yuko Fujiwara; Amin Al-Shami; Tamas Oravecz; Gabor Tigyi; Roberta Pelanda; Raul M. Torres
• Keywords: Cancer Immunotherapy; Tumor progression

Abstract CD8 T lymphocytes are able to eliminate nascent tumor cells through a process referred as immunosurveillance. However, multiple inhibitory mechanisms within the microenvironment have been described that impede rejection by cells, including increased signaling receptors. Lysophosphatidic acid (LPA) is bioactive lysophospholipid has shown repeatedly promote diverse cellular processes benefiting tumorigenesis. Accordingly, exaggerated expression of LPA and receptors common feature cell lineages can result in elevated systemic levels. recognized at least six distinct G protein–coupled receptors, several which expressed although precise function T-cell activation not defined. Here, we show via LPA5 receptor suppresses antigen signaling, activation, proliferation vitro vivo. Importantly, mouse melanoma model tumor-specific LPA5-deficient control growth significantly better than wild-type cells. Together, these data suggest production tumors serves only an autocrine manner tumorigenesis, but also mechanism suppress adaptive immunity highlights potential novel target for cancer treatment. Cancer Immunol Res; 1(4); 245–55. ©2013 AACR.