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