Journal
JOURNAL OF IMMUNOLOGY
Volume 196, Issue 1, Pages 64-71Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1402664
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Funding
- National Cancer Institute [R01CA108609]
- Swiss National Science Foundation [310030_126995]
- Institute of Arthritis Research
- Carlos and Elsie de Reuter Foundation
- NATIONAL CANCER INSTITUTE [R01CA101741, R01CA108609] Funding Source: NIH RePORTER
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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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