The Tumor Antigen NY-ESO-1 Mediates Direct Recognition of Melanoma Cells by CD4+ T Cells after Intercellular Antigen Transfer.

Jean Francois Fonteneau, Fabienne Brilot, Christian Münz, Monique Gannagé

Journal: Journal of immunology (Baltimore, Md. : 1950) 2016;196(1):64-71

PMID: 26608910

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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.

Address: INSERM UMR892, CNRS UMR6299, Université de Nantes, Nantes 44007, France;; Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, St. Westmead, New South Wales 2145, Australia;; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich 8006, Switzerland;; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich 8006, Switzerland; Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva 1211, Switzerland; and Division of Rheumatology, Department of Internal Medicine, University Hospital, Geneva 1205, Switzerland [email protected].

DOI: 10.4049/jimmunol.1402664