Depletion of plasmacytoid dendritic cells and HIF-1α inhibition enhance immunotherapy against hepatocellular carcinoma
نویسندگان
چکیده
Abstract Hepatocellular Carcinoma (HCC) is one of the deadliest forms cancer. Recent years have seen significant advances for HCC treatment, but up to 70% patients remain at high risk recurrence necessitating urgent need more effective therapies. Plasmacytoid dendritic cells (pDCs) heavily infiltrate liver tumor tissues, contribute an immunosuppressive microenvironment (TEM), and promote growth. Furthermore, hypoxia often occurs in tissues plays central role TME. A hypoxic TME enhances pDC recruitment into via upregulation hypoxia-inducible factor 1α (HIF-1α). Here we show that distribution pDCs does not co-localized with areas HCC. In immunocompetent mouse model, depletion using antibody or HIF-1α inhibitor echinomycin significantly suppressed The combination inhibition growth effectively. Both treatments reshaped changes cytokine profile increased tumor-infiltrating CD8 T cells. Reduced basic helix-loop-helix transcription E2-2 expression by abrogated protumor functions resulting reactivating tumor-reactive This study demonstrates targeting both may serve as immunotherapy
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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.245.18