Dual Effects of Cellular Immunotherapy in Inhibition of Virus Replication and Prolongation of Survival in HCV-Positive Hepatocellular Carcinoma Patients

Abstract

Immune cells play an important role in the development and progression of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). We conducted a retrospective study to evaluate the influence of adoptive cellular immunotherapy (CIT) on viral load and progression-free survival (PFS) for HCC patients infected with HCV. Patients (n = 104) were divided into a control group (conventional therapy, n = 73) and study group (combination of CIT and conventional therapy, n = 31). Autologous mononuclear cells were induced into natural killer, γδT, and cytokine-induced killer cells and infused intravenously to study group patients. More patients had shown viral load decrease or were stable in study group (100% versus 75%) (p = 0.014). The median PFS of the study group and control group was 16 and 10 months, respectively (p = 0.0041), and only CIT was an independent prognostic factor for PFS (hazard ratio, 0.422; p = 0.005). Three patients developed transient moderate fever after infusion, and there were no significant differences in alanine aminotransferase and aspartate aminotransferase levels before and after treatment in both groups. Our results show that CIT contributes to improvement of prognosis and inhibition of viral replication in HCV-related HCC patients, without impairment of liver function.

Immunotherapy with dendritic cells and cytokine-induced killer cells for hepatocellular carcinoma: A meta-analysis

“…None of the studies reported immunotherapy-related hospital mortality. Only 23 patients in four studies[23,29,32,36] were reported with grade III or IV adverse events. Fever was addressed as the most common event after immunotherapy.…”

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

“…Even though gene modification approaches, such as CAR technology, have achieved ground-breaking success in CD19+ diseases, [3][4][5] the application of such a strategy in solid tumors is still under continuous investigation. Notably, the published literature has intensively reviewed the clinical potential of Vγ9Vδ2 T cells as a new strategy for cancer immunotherapy; [13][14][15]22,23 for instance, previous clinical trials on non-small cell lung cancer, 10,46 hepatocellular carcinoma 47 renal cell carcinoma, [48][49][50][51] and myeloma 52 proved the feasibility of Vγ9Vδ2 T cells in tumor immunotherapy. However, limited clinical efficacy 26 makes Vγ9Vδ2 T cells of modest value in clinical investigation and application.…”

Diverse Functions of γδ T Cells in the Progression of Hepatitis B Virus and Hepatitis C Virus Infection

“…Zoledronate induces the proliferation of γδ T cells in HCC patients who exhibit upregulated expression of IFN-γ, TNF-α, GrB, perforin, and lysosome-associated membrane protein 1 ( 47 ). A clinical trial has shown that the combined use of γδ T cells, NK cells, and cytokine-induced killer (CIK) therapy significantly inhibits virus replication and prolongs the survival rate of HCV-positive HCC patients ( 21 ).…”

“…Similar contradictory functions are also observed in other stages. In HCC, human Vδ2 T cells, which can be activated and proliferate in vitro ( 20 ), are used in the clinic to prolong the survival time of HCC patients ( 21 ).…”