Fig. 3.
Mechanisms of tumor immune escape. ‘Hot’ tumors (A) may escape through up-regulation of immune checkpoint molecules and Tregs, secretion of immunosuppressive factors, indoleamine-2,3-dioxygenase (IDO), or T-cell anergy. (B) Tumor intrinsic mechanism of escape in “cold tumors” by downregulation of MHC molecules, attraction of M2 tumor-associated macrophages (TAMs), alteration of the tumor microenvironment, discouraging T-cell homing either by subduing inflammation, or suppressing release of T-cell chemokines, or releasing inhibitory cytokines to impair the recruitment of immune cells to the tumor microenvironment, or by dysregulating oncogene pathways including PI3 kinase/PTEN/AKT, p53 and STAT3 signaling.