012 CD4+ T cells control immune evasive tumors by reprogramming myeloid cells in an IFN-dependent manner

نویسندگان

چکیده

Modern cancer immunotherapies largely focus on the ability of CD8+ cytolytic T cells to directly recognize and kill tumor cells. These strategies are limited by development an immunosuppressive microenvironment emergence immune evasive MHC-deficient or IFN-unresponsive CD4+ effector can contribute responses independent However, potential mechanisms cell-mediated anti-tumor immunity remain elusive. Using adoptive cell therapy model, we show how indirect mode action empowers destruction melanomas that escape direct targeting. Despite their relatively low abundance, control resist therapy. This is due synergize with innate stimuli reprogram tumor-associated inflammatory myeloid network towards IFN-activated antigen-presenting tumoricidal iNOS-expressing phenotypes. IFNg blockade during profoundly abrogated this reprogramming cells, particularly generation nitric oxide-secreting monocytes. Simultaneous oxide inhibition treatment demonstrates indirectly through IFN-dependent activation production oxide. Together, our data orchestrate killing tumors complements activity advance immunotherapies.

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ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2023

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2023.03.013