TIM-3 (T cell immunoglobulin and mucin domain-3), also known as HAVCR2 is an immunosuppressive protein that enhances tolerance and inhibits anti-tumor immunity. It is upregulated on several populations of activated myeloid cells (macrophage, monocyte, dendritic cell, microglia, mast cell) and T cells (Th1, CD8+, NK, Treg). TIM-3 ligation by Galectin-9 attenuates CD8+ and Th1 cell responses and promotes the activity of Treg and myeloid derived suppressor cells. Dendritic cell-expressed TIM-3 dampens inflammation by enabling the phagocytosis of apoptotic cells and the cross-presentation of apoptotic cell antigens. TIM-3 also binds the alarmin HMGB1, thereby preventing the activation of TLRs in response to released tumor cell DNA.