{Reference Type}: Journal Article
{Title}: LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice.
{Author}: Mulholland M;Kritikou E;Katra P;Nilsson J;Björkbacka H;Lichtman AH;Rodriguez A;Engelbertsen D;
{Journal}: JACC CardioOncol
{Volume}: 4
{Issue}: 5
{Year}: Dec 2022
{Factor}: 8.422
{DOI}: 10.1016/j.jaccao.2022.09.005
{Abstract}: <B>UNASSIGNED: </B>The immune checkpoint receptor lymphocyte-activation gene 3 (LAG3) is a new target for immune checkpoint blockade (ICB), but the effects of LAG3 on atherosclerosis are not known.<BR><B>UNASSIGNED: </B>The aim of the study was to evaluate the role of LAG3 on plaque inflammation using murine hypercholesterolemic models of atherosclerosis.<BR><B>UNASSIGNED: </B>To study the role of LAG3 in atherosclerosis, we investigated both bone marrow chimeras lacking LAG3 in hematopoietic cells as well as global Lag3 -/- knockout mice. Effects of anti-LAG3 monoclonal antibody monotherapy and combination therapy with anti-programmed cell death protein 1 (PD-1) were tested in hypercholesterolemic low-density lipoprotein receptor knockout (Ldlr -/- ) mice and evaluated by histology and flow cytometry.<BR><B>UNASSIGNED: </B>LAG3-deficiency or treatment with blocking anti-LAG3 monoclonal antibodies led to increased levels of both interferon gamma-producing T helper 1 cells and effector/memory T cells, balanced by increased levels of regulatory T cells. Plaque size was affected by neither LAG3 deficiency nor LAG3 blockade, although density of T cells in plaques was 2-fold increased by loss of LAG3. Combination therapy of anti-PD-1 and anti-LAG3 had an additive effect on T cell activation and cytokine production and promoted plaque infiltration of T cells.<BR><B>UNASSIGNED: </B>Loss of LAG3 function promoted T cell activation and accumulation in plaques while not affecting plaque burden. Our report supports further clinical studies investigating cardiovascular risk in patients treated with anti-LAG3 ICB.