Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy

Table 2 Clinical trials by targeting regulatory T cells to modulate the immune response

Trial	Phase	Treatment	Results	Ref.
NCT02476123	I	Anti-CCR4 antibody mogamulizumab	Treg depletion induced by anti-CCR4 antibody (mogamulizumab), in combination with anti-PD-1 antibody (nivolumab) showed antitumor activity and increased CD8+ T cell infiltration	Doi et al[78], 2019; Sánchez-Fueyo et al[83], 2020
NCT02166177	I	Intravenous infusion of ex vivo expanded Tregs	Treg transfer can transiently increase circulating Tregs and inhibit anti-donor T cell responses in patients with liver transplants	Fueyo et al[83], 2020
NCT02166177	I	Autologous Treg therapy	To defect safety and efficacy study of regulatory T cell therapy in liver transplant patients	Whitehouse et al[84], 2017
NCT01624077	I	Injection of Tregs	To defect safety and efficacy study of regulatory T cell therapy in liver transplant patients	Whitehouse et al[84], 2017
NCT03654040	I	A single dose of alloantigen-reactive Tregs (arTreg) (≥ 90 × 106 total cells)	It is a single-center, prospective, open-label, non-randomized clinical trial exploring cellular therapy to facilitate immunosuppression withdrawal in liver transplant recipients	Cvetkovski et al[85], 2021
NCT03577431		arTreg-CSB (2.5 × 106 cells)
NCT02260375	I	Infusion of mesenchymal stromal cells	MSC infusion in liver transplant recipients slightly increased circulating Treg/memory Treg over baseline, without a statistically significant, but not in the control group	Casiraghi et al[86], 2021
NCT02027116	I	DNA vaccine GLS-6150	GLS-6150 decreases Treg cell frequency and enhances HCV-specific T cell responses without significant side effects	Han et al[87], 2020
NCT02174276	II	GS-4774, a yeast-based therapeutic vaccine	Treatment with GS-4774 increased T-cell functions by increasing the production of IFN-γ and TNF and reducing the cell number of Tregs	Boni et al[88], 2019
NCT02360592	IV	Combined therapy with interferon plus IL-1 and hepatitis B Vaccine	Combination therapy increased the level of hepatitis B surface antigen with partial restoration of Tregs and NK cells	Wu et al[89], 2019
NCT02072486	None	Sorafenib, a multiple kinase inhibitor	Treatment with sorafenib can significantly suppress extracellular signal-regulated kinases+ FMS-like tyrosine kinase 3+ Tregs and myeloid-derived suppressor cells to benefit the survival of HCC patients	Kalathil et al[90], 2019

CCR: C-C chemokine receptor; CSB: Co-stimulatory blockade; PD-1: Programmed cell death protein 1; Treg: Regulatory T cells; MSC: Mesenchymal stromal cells; DNA: Deoxyribonucleic acid; GLS: Glutaminase; IFN: Interferon; TNF: Tumor necrosis factor; IL: Interleukin; NK: Natural killer; FMS: Feline McDonough sarcoma.