title: The Tumor Antigen NY-ESO-1 Mediates Direct Recognition of Melanoma Cells by CD4+ T Cells after Intercellular Antigen Transfer.
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.
authors.affiliation: INSERM UMR892, CNRS UMR6299, Université de Nantes, Nantes 44007, France;
authors.forename: Jean Francois
authors.identifier: http://orcid.org/0000-0002-3284-8319
authors.initials: JF
authors.lastname: Fonteneau
authors.affiliation: 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;
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot
authors.affiliation: Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich 8006, Switzerland;
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.affiliation: 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 monique.ghannage@unige.ch.
authors.forename: Monique
authors.identifier: http://orcid.org/0000-0003-3533-1937
authors.initials: M
authors.lastname: Gannagé
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001343:Autophagy / Q000276:immunology; D000071192:Autophagy-Related Protein 12; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007976:Leupeptins; D008213:Lymphocyte Activation / Q000276:immunology; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008565:Membrane Proteins / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics
chemical_list: C466624:ATG12 protein, human; D000951:Antigens, Neoplasm; D000071192:Autophagy-Related Protein 12; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C497811:LAMP2 protein, human; D007976:Leupeptins; D052119:Lysosomal-Associated Membrane Protein 2; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D025841:Small Ubiquitin-Related Modifier Proteins; C067713:lactacystin; D002738:Chloroquine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine