Figure 2.

The tumor-immunity cycle and three immunophenotypes. Antitumor immunity is mediated to a large extent by CD8⁺ T lymphocytes. The tumor-immunity cycle consists of the following steps: (1) tumor antigen release, (2) tumor antigen processing and presentation, (3) T-cell priming and activation, (4) trafficking of T lymphocytes through the bloodstream to tumors, (5) infiltration of T lymphocytes into the tumor parenchyma from the vasculature or tumor periphery, (6) recognition of tumor cells, and (7) cytotoxic T lymphocyte (CTL) destruction of tumor cells by granule exocytosis or through the Fas/FasL pathway. Dead tumor cells release additional antigens, allowing the tumor-immunity cycle to continue. Notably, tumors with the immune-desert phenotype (yellow) cannot pass steps 1-3 due to the absence of T lymphocytes in both the tumor and its margins. Tumors with the immune-excluded phenotype (blue) cannot exceed steps 4-5 due to a lack of T lymphocytes in the tumor bed. Tumors with the immune-inflamed phenotype (red) cannot exceed steps 6-7 due to T-cell exhaustion and checkpoint activation. Adapted with permission from ¹¹, copyright 2013 Elsevier.