T-bet transduction enhances anti-tumor efficacy of IFN-producing dendritic cell (IKDC) against hepatocellular carcinoma via apoptosis induction.

Biochem Biophys Res Commun

Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, China; Department of General Surgery, Guangdong Second Provincial General Hospital, Southern Medical University, Guangzhou 510317, China. Electronic address:

Published: January 2021

Hepatocellular carcinoma (HCC) remains a public health challenge that requires dedication to develop new treatment options due to its high recurrence rate and poor prognosis. Interferon-producing killer dendritic cell (IKDC) is a subset of INF-γ secreting immune cells that modulates acquired immunity and possesses cytolytic ability. We modified IKDC isolated from the murine spleen with T-bet lentiviral transduction to enhance its cytotoxicity against HCC, and acquired IKDC overexpressing T-bet (T-bet-IKDC) for the first time. T-bet-IKDC has increased INF-γ secretion and surface expression of NKG2D and TRAIL. In vitro study by MTS assay and flow cytometry showed enhanced anti-tumor effect against H22 cells via apoptosis induction in a dose- and time-dependent manner. In vivo study on H22-bearing mice confirmed increased INF-γ secretion, reduced tumor size, increased caspase 3 cleavage, and up-regulation of cytotoxic molecules after T-bet-IKDC administration. The study suggested prospective application of T-bet-IKDC in future immunotherapy for HCC treatment.

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http://dx.doi.org/10.1016/j.bbrc.2020.11.118DOI Listing

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