Tumor-Infiltrating mregDCs Restrain Anti-Tumor Immunity in Early Relapse HCC - PubMed
3 hours ago
- #TNFR2 blockade
- #HCC relapse
- #mregDCs
- A dendritic cell subset DC3, identified as mature regulatory DCs (mregDCs) enriched in immunoregulatory molecules, is found in relapsed hepatocellular carcinoma (HCC) and restrains anti-tumor immunity.
- MregDCs recruit dysfunctional CD161+CD8+ T cells that secrete TNF-α, activating the non-canonical NF-κB pathway via tumor necrosis factor receptor 2 (TNFR2) to promote mregDC differentiation.
- In vivo mouse models show dual blockade of TNFR2 and PD-L1 reduces tumor burden more effectively than anti-PD-L1 monotherapy in mregDC-rich HCC, highlighting TNFR2 as a therapeutic target.
- Strong interactions exist between mregDCs and FCN1+ monocytes, a myeloid-derived suppressor cell (MDSC)-like population, contributing to an immunosuppressive network in relapse HCC.