Fig. 2

Tumor microenvironment consists of malignant cells, stroma and different populations of immune cells. Complex crosstalk between them shapes the final outcome of neoplastic disease. Anticancer response is driven mainly by cytotoxic CD8⁺ T cells and NK cells, which release IFN-γ and granzymes, thus are involved in direct lysis of the tumor cells. Th1 subpopulation of CD4⁺ T cells, M1 macrophages and activated dendritic cells (DCs) support anticancer immunity by antigen presentation and cytokine production (IL-12, IFN-γ). CD8⁺ and CD4⁺ T cells recognize tumor antigens in the context of MHC class I and II respectively, followed by costimulatory signaling via CD28 molecule, necessary for their full activation, proliferation and function. Tumor progression, in turn, is associated with the presence of the Th2 and T regulatory CD4⁺ lymphocytes, M2 macrophages and MDSC. These cells secrete immunosuppressive factors such as IL-4, IL-10, or TGF-β and exhibit high activity of arginase, respectively. Unresponsiveness of cytotoxic CD8⁺ T cells is caused by decreased expression of MHC I on the cancer cells surface and activation of coinhibitory receptors such as PD-1. Adapted from Servier Medical Art