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

Bawden, EG; Wagner, T; Schr&#246;der, J; Effern, M; Hinze, D; Newland, L; Attrill, GH; Lee, AR; Engel, S; Freestone, D; de Lima Moreira, M; Gressier, E; McBain, N; Bachem, A; Haque, A; Dong, R; Ferguson, AL; Edwards, JJ; Ferguson, PM; Scolyer, RA; Wilmott, JS; Jewell, CM; Brooks, AG; Gyorki, DE; Palendira, U; Bedoui, S; Waithman, J; Hochheiser, K; H&#246;lzel, M; Gebhardt, T

Author(s): Bawden, EG; Wagner, T; Schröder, J; Effern, M; Hinze, D; Newland, L; Attrill, GH; Lee, AR; Engel, S; Freestone, D; de Lima Moreira, M; Gressier, E; McBain, N; Bachem, A; Haque, A; Dong, R; Ferguson, AL; Edwards, JJ; Ferguson, PM; Scolyer, RA; Wilmott, JS; Jewell, CM; Brooks, AG; Gyorki, DE; Palendira, U; Bedoui, S; Waithman, J; Hochheiser, K; Hölzel, M; Gebhardt, T;
Details: Publication Year 2024-01-19,Volume 9,Issue #91,Page eadi9517
Journal Title: Science Immunology
Publication Type: Research article
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 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.
Publisher: American Association for the Advancement of Science
Keywords: Humans; *Melanoma; *Skin Neoplasms; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Histocompatibility Antigens Class II; HLA Antigens
Department(s): Surgical Oncology
Publisher's Version: https://doi.org/10.1126/sciimmunol.adi9517
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-01-30 06:24:20

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