B16 melanomas evade antitumor immunity by the loss of epitope presentation and the acquisition of tumor resistance to granzyme B.

Melanomas exhibit the highest rate of heterogeneity among cancer cell types. In this study, we tested the two types of B16 melanoma cells (B16-S0-1 and B16-S1-1) showing resistance to antitumor immunity. These cells expressed Trp2 protein. Contrary to B16 and B16-S0-1 cells, B16-S1-1 cells failed to stimulate IFN-γ responses in Trp2-specific CD8+ T cells, suggesting that B16-S1-1 cells may have lost the ability to present antigen to Ag-specific CTLs in the context of MHC class I molecules. However, B16-S0-1 cells exhibited active Stat3 and decreased Bcl-2 expression, which were found to be not associated with immune escape. B16-S0-1 cells were more resistant to granzyme B-mediated caspase activation and apoptosis than B16 cells. Thus, these data show that B16 cells escape antitumor immune responses through the loss of epitope presentation to CTLs and the acquisition of tumor cell resistance to granzyme B-mediated caspase activation.