Global inhibition of Ly-49/MHC-I interactions by anti-MHC-I augments innate and adaptive immunity against cancer metastasis.
نویسندگان
چکیده
Abstract We have identified an pan-anti-MHC-I mAb (M1/42), which blocks the interaction of NK cell inhibitory receptors (Ly-49 antigens) with MHC-I, but does not inhibit antigen presentation by MHC-I. Administration M1/42 in vivo markedly activated IFNg-producing cells. cell-derived IFNg stimulated APC to produce IL-12/-15/-18 cytokine cascades that further drove proliferation cells and memory phenotype (MP) T treatments profoundly augmented innate adaptive immunity against PD-1-sensitive -resistant transplanted tumors. Given are critical control cancer metastases, we evaluated effects therapy several metastatic models. successfully constrained B16F10 lung metastasis enhancing CD8 +T infiltration inducing melanoma-specific MP expansion activation. In contrast, treatment conventional checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4 anti-NKG2A) had no therapeutic effect. scRNAseq analysis melanoma tumor infiltrating lymphocytes revealed significantly enhanced expression multiple genes associated also Th1-type immune responses, greatly restricted liver produced pancreatic adenocarcinoma line via intrasplenic or intravenous injection. Thus, global inhibition Ly-49/MHC-I interactions results activation a potent response restrains growth both tumors injection This work was supported Intramural Research Program NIAID, NIH.
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.245.08