CD4 T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses

EG Bawden; T Wagner; J Schröder; M Effern; D Hinze; L Newland; GH Attrill; AR Lee; S Engel; D Freestone; M de Lima Moreira; E Gressier; N McBain; A Bachem; A Haque; R Dong; AL Ferguson; JJ Edwards; PM Ferguson; RA Scolyer; JS Wilmott; CM Jewell; AG Brooks; DE Gyorki; U Palendira; S Bedoui; J Waithman; K Hochheiser; M Hölzel; T Gebhardt

Journal article

CD4 T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses

EG Bawden, T Wagner, J Schröder, M Effern, D Hinze, L Newland, GH Attrill, AR Lee, S Engel, D Freestone, M de Lima Moreira, E Gressier, N McBain, A Bachem, A Haque, R Dong, AL Ferguson, JJ Edwards, PM Ferguson, RA Scolyer Show all

Science Immunology | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2024

DOI: 10.1126/sciimmunol.adi9517

Download PDF

Abstract

Whereas CD4+ T cells conventionally mediate antitumor immunity by providing help to CD8+ T cells, recent clinical studies have implied an important role for cytotoxic CD4+ T cells in cancer immunity. Using an orthotopic melanoma model, we provide a detailed account of antitumoral CD4+ T cell responses and their regulation by major histocompatibility complex class II (MHC II) in the skin. Intravital imaging revealed prominent interactions of CD4+ T cells with tumor debris-laden MHC II+ host antigen-presenting cells that accumulated around tumor cell nests, although direct recognition of MHC II+ melanoma cells alone could also promote CD4+ T cell control. CD4+ T cells stably suppressed or erad..

View full abstract

University of Melbourne Researchers

Teagan McGivern Author

Jan Schroeder Author

Ariane Lee Author

Sven Engel Author

Related Projects (2)

MICROBIOTA AND T CELL IMMUNITY

Our research has identified unprecedented communications between the microbes that colonize our body’s surfaces and killer T cell immunity. ..

UNDERSTANDING IMMUNE MECHANISMS THAT DRIVE EFFICIENT MELANOMA SUPPRESSION

Novel cancer therapies aimed at stimulating the body's immune defence have shown remarkable clinical success, although the immune mechanisms..

Grants

Awarded by Cancer Council Victoria

Funding Acknowledgements

T.G. is supported by an investigator Fellowship from the National Health and Medical Research Council Australia (NHMRC, APP1194482). this work was further supported by research grants from the NHMRC (APP1187068, APP1124815, and APP2008408) and the Cancer Council Victoria (APP1163465), a 350th anniversary Research grant from Merck KGGA and the International Research Training Group (IRTG2168) funded by the German Research Council and the University of Melbourne. the project was also supported by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) within GRK 2168 and Germany's Excellence Strategy-EXC2151-390873048. J.W. was supported by the Cancer Council Western Australia. K.h. was supported by the Rhian and Paul Brazis Fellowship in Translational Melanoma Immunology, administered by the Peter Maccallum Cancer Foundation. this work was supported by a National Health and Medical Research Council of Australia (NHMRC) Program grant (APP1093017) to R.a.S. g.h.a. was supported by scholarships from the University of Sydney and by the Janet Ferguson Mia PhD Scholarship. P.m.F. was supported by the Mcmurtrie Cancer Pathology Fellowship and the Melanoma Institute Australia. J.S.W. is supported by an NHMRC Investigator Fellowship (APP1174325), Melanoma Research Alliance Young Investigator Fellowship (#700455), Cancer Institute NSW (TPG2114), and the University of Sydney. R.a.S. is supported by a National Health and Medical Research Council of Australia (NHMRC) Investigator grant (2022/GNT2018514). Support from the Ainsworth Foundation, the Clearbridge Foundation, the Cameron Family, and the Lady Mary Fairfax Charitable Trust to the Melanoma Institute Australia are also gratefully acknowledged.