PDF file - 77KB, VISTA does not affect B cell proliferation. CD19 positive B cells were purified from human PBMCs by magnetic bead negative selection. (a and b) cells were stimulated in the presence of VISTA-Ig (a) or control Ig (b) at 5ug/ml for 4 days with 250ng/ml of CD40 agonist. Plots show representative CFSE profiles gated on live CD19 positive events. C) percent proliferation in the presence of decreasing concentrations of agonist in the presence of VISTA-Ig (filled bars) or control Ig (open bars) at 5ug/ml for 4 days. Data is representative of 3 separate experiments.
ARTICLE ABSTRACTV-domain Ig suppressor of T cell activation (VISTA) is a potent negative regulator of T-cell function that is expressed on hematopoietic cells. VISTA levels are heightened within the tumor microenvironment, in which its blockade can enhance antitumor immune responses in mice. In humans, blockade of the related programmed cell death 1 (PD-1) pathway has shown great potential in clinical immunotherapy trials. Here, we report the structure of human VISTA and examine its function in lymphocyte negative regulation in cancer. VISTA is expressed predominantly within the hematopoietic compartment with highest expression within the myeloid lineage. VISTA-Ig suppressed proliferation of T cells but not B cells and blunted the production of T-cell cytokines and activation markers. Our results establish VISTA as a negative checkpoint regulator that suppresses T-cell activation, induces Foxp3 expression, and is highly expressed within the tumor microenvironment. By analogy to PD-1 and PD-L1 blockade, VISTA blockade may offer an immunotherapeutic strategy for human cancer. Cancer Res; 74(7); 1924–32. ©2013 AACR.