التفاصيل البيبلوغرافية
| العنوان: |
CD4+ T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses. |
| المؤلفون: |
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. |
| المصدر: |
Science Immunology; 2024, Vol. 9 Issue 91, p1-18, 18p |
| مصطلحات موضوعية: |
T cells, CYTOTOXIC T cells, NITRIC-oxide synthases, MYELOID cells, MAJOR histocompatibility complex, HUMORAL immunity, GRAFT versus host reaction |
| مستخلص: |
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. Editor's summary: CD4+ T cells have been primarily appreciated for their helper functions in antitumor immune responses, but the extent to which they directly contribute to tumor killing remains unclear. Using a mouse model of cutaneous melanoma, Bawden et al. characterized the effector functions of CD4+ T cells in generating protective antitumor immunity. Melanoma-specific CD4+ T cells infiltrated tumors, adopted diverse effector states, and could provide tumor protection independent of other lymphocytes. Whereas MHC II expression by melanoma cells was sufficient to activate protective CD4+ T cell–mediated immunity, host antigen-presenting cells could also drive protection. CD4+ T cells provided protection through multiple partially redundant cytotoxicity pathways, including TNF and Fas ligand, but also by activating IFN-γ–dependent nitric oxide production in myeloid cells. Together, these results demonstrate that tumor-infiltrating CD4+ T cells are equipped to contribute to tumor control through multiple helper and effector modes. —Claire Olingy [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
