Mechanisms of endogenous MHC class II presentation by tumor cells

Evaluation of: Tsuji T, Matsuzaki J, Caballero OL et al. Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells. J. Immunol. 188, 3851-3858 (2012). In this study, Tsuji and colleagues investigated how tumor antigen NY-ESO-1 was processed by melanoma cells and subsequently presented on HLA class II for the recognition of NY-ESO-1-specific CD4(+) T cells. Using a combination of specific inhibitors and RNAi techniques, they found that tumor cells utilize a novel peptide selective antigen presentation pathway that requires both proteasome and endosomal protease-dependent processing, as well as heat-shock protein 90-dependent chaperoning. This newly described tumor-specific, endogenous MHC class II antigen presentation could have an impact on both antitumor or protumor T-cell responses.