1238 Local differentiation of Tcf7+ stem-like CD8+ T cells into activating effector CD8+ T cells is critical for antitumor effects induced by intratumoral injection of immunogenic recombinant modified vaccinia virus ankara
نویسندگان
چکیده
Immunogenic non-replicative recombinant modified vaccinia virus Ankara (rMVA) has been developed to turn "cold" tumors into "hot" tumors. MVAΔE5R-hFlt3L-mOX40L is our first-generation rMVA by deleting a cGAS (cyclic GMP-AMP synthase) inhibitor encoded the E5R gene and inserting human Flt3L (a growth factor for dendritic cells) murine OX40L co-stimulatory molecule T cells). In this study, we used combined single-cell RNA sequencing (scRNA-seq) TCR (scTCR-seq) strategy elucidate how IT affects transcriptome proliferation of CD8+ cells in injected We performed scRNA-seq scTCR-seq sorted from B16-F10 melanomas treated with C57BL/6J mice identified six clusters intratumoral cells, including Tcf7+CD62L+ (C0), Tcf7+CD62L- (C1), Proliferating Toxint (C2), effector-like Toxlow (C3), (C4), exhausted Toxhi (C5). resulted reduction stem-like (C0 C1) (C5) expansion proliferating (C2, C3, C4). revealed that PBS mock-treated tumors, most expanded clones were C5, whereas rMVA-treated C2 C4 had highest clonal expansion. Depleting Tcf7+ antitumor effects response treatment. These results demonstrate promotes tumor-infiltrating CD8+T cell differentiation, expansion, activation.
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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.2023.03.1252