Lag3 is expressed on macrophages in the tumor microenvironment 2761

Description Immunotherapies that target immune checkpoints have extensively been shown to reverse immune cell exhaustion, however patient responses to immune checkpoint inhibitors remain heterogeneous. Lymphocyte-activating gene 3 (Lag3) has recently emerged as a promising and potent checkpoint inhibitor expressed on various immune cells. While research studies have focused on the role of Lag3 in T cell exhaustion, questions remain regarding Lag3 biology and expression. Here, we have identified tumor associated macrophages as an additional Lag3 expressing immune cell in a tumor microenvironment. In an effort to further explore this, M1- and M2-like bone marrow derived macrophages were stimulated with IFNγ and IL-4, respectively, and shown to have upregulated Lag3 expression after 24 hours. Specifically, M1-like macrophages showed variable expression of Lag3, with an initial upregulation at 4 hours, but subsequently reduced to a baseline level resembling that of unstimulated macrophages. However, M2-like macrophages maintained high Lag3 expression over a prolonged period of time. Interestingly, M2-like macrophage Lag3 expression seems to be glycolysis dependent because incubation with the inhibitor, 2-DG, reduced expression on M2-like macrophages, but only minimally affected levels on M1 macrophages. The dynamic expression of Lag3 by macrophages indicates that this immune population may serve as a potential therapeutic target in cancer. Funding Sources Supported by T32CA009592.