[HTML][HTML] The tumor antigen NY-ESO-1 mediates direct recognition of melanoma cells by CD4+ T cells after intercellular antigen transfer

JF Fonteneau, F Brilot, C Münz… - The Journal of …, 2016 - journals.aai.org
The Journal of Immunology, 2016journals.aai.org
Abstract NY-ESO-1–specific CD4+ T cells are of interest for immune therapy against tumors,
because it has been shown that their transfer into a patient with melanoma resulted in tumor
regression. Therefore, we investigated how NY-ESO-1 is processed onto MHC class II
molecules for direct CD4+ T cell recognition of melanoma cells. We could rule out
proteasome and autophagy-dependent endogenous Ag processing for MHC class II
presentation. In contrast, intercellular Ag transfer, followed by classical MHC class II Ag …
Abstract
NY-ESO-1–specific CD4+ T cells are of interest for immune therapy against tumors, because it has been shown that their transfer into a patient with melanoma resulted in tumor regression. Therefore, we investigated how NY-ESO-1 is processed onto MHC class II molecules for direct CD4+ T cell recognition of melanoma cells. We could rule out proteasome and autophagy-dependent endogenous Ag processing for MHC class II presentation. In contrast, intercellular Ag transfer, followed by classical MHC class II Ag processing via endocytosis, sensitized neighboring melanoma cells for CD4+ T cell recognition. However, macroautophagy targeting of NY-ESO-1 enhanced MHC class II presentation. Therefore, both elevated NY-ESO-1 release and macroautophagy targeting could improve melanoma cell recognition by CD4+ T cells and should be explored during immunotherapy of melanoma.
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