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

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 a...

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Vydáno v:	Science immunology Ročník 9; číslo 91; s. eadi9517
Hlavní autoři:	Bawden, Emma G, Wagner, Teagan, Schröder, Jan, Effern, Maike, Hinze, Daniel, Newland, Lewis, Attrill, Grace H, Lee, Ariane R, Engel, Sven, Freestone, David, de Lima Moreira, Marcela, Gressier, Elise, McBain, Nathan, Bachem, Annabell, Haque, Ashraful, Dong, Ruining, Ferguson, Angela L, Edwards, Jarem J, Ferguson, Peter M, Scolyer, Richard A, Wilmott, James S, Jewell, Christopher M, Brooks, Andrew G, Gyorki, David E, Palendira, Umaimainthan, Bedoui, Sammy, Waithman, Jason, Hochheiser, Katharina, Hölzel, Michael, Gebhardt, Thomas
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 19.01.2024
Témata:	CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Histocompatibility Antigens Class II HLA Antigens Humans Melanoma Skin Neoplasms
ISSN:	2470-9468, 2470-9468
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Shrnutí:	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 eradicated tumors even in the absence of other lymphocytes by using tumor necrosis factor-α and Fas ligand (FasL) but not perforin-mediated cytotoxicity. Interferon-γ was critical for protection, acting both directly on melanoma cells and via induction of nitric oxide synthase in myeloid cells. Our results illustrate multifaceted and context-specific aspects of MHC II-dependent CD4 T cell immunity against cutaneous melanoma, emphasizing modulation of this axis as a potential avenue for immunotherapies.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2470-9468 2470-9468
DOI:	10.1126/sciimmunol.adi9517