Combinational immune-cell therapy of natural killer cells and sorafenib for advanced hepatocellular carcinoma: a review

Abstract

BackgroundHigh prevalence of hepatocellular carcinoma (HCC) and typically poor prognosis of this disease that lead to late stage diagnosis when potentially curative therapies are least effective; therefore, development of an effective and systematic treatment is an urgent requirement.Main bodyIn this review, several current treatments for HCC patients and their advantages or disadvantages were summarized. Moreover, various recent preclinical and clinical studies about the performances of “two efficient agents, sorafenib or natural killer (NK) cells”, against HCC cells were investigated. In addition, the focus this review was on the chemo-immunotherapy approach, correlation between sorafenib and NK cells and their effects on the performance of each other for better suppression of HCC.ConclusionIt was concluded that combinational therapy with sorafenib and NK cells might improve the outcome of applied therapeutic approaches for HCC patients. Finally, it was also concluded that interaction between sorafenib and NK cells is dose and time dependent, therefore, a careful dose and time optimizing is necessary for development of a combinational immune-cell therapy.

Sorafenib Induces Pyroptosis in Macrophages and Triggers Natural Killer Cell–Mediated Cytotoxicity Against Hepatocellular Carcinoma

“…Furthermore, inhibition of MHC class I polypeptide‐related sequence A (MICA) shedding by sorafenib may bolster an antitumoral NK‐cell response because MICA, a ligand for the NK‐cell activating receptor NKG2D, is subsequently more highly expressed on the tumor cell surface and thus recognized by NK cells, leading to their activation . The role of these cells in HCC progression points to an NK cell–based therapy for HCC patients in order to overcome tumor‐induced immune tolerance . Taken together, sorafenib potentiates an effective immunotherapy and, furthermore, does not trigger immune‐related adverse effects such as cytokine release syndrome .…”

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

“…International Publisher sorafenib has become the first-line treatment and made the long-term survival of patients possible to some extent. Even so, with the problems of disease progression, drug-resistance, and adverse drug reaction as the therapy progresses, the urgent need for a more potent novel, targeted drug to replace sorafenib remains an increasingly prominent issue [11][12][13][14][15].…”

Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma

“…The function of NK cells against tumor cells is through various mechanisms including releasing cytoplasmic granules (such as Perforin and Granzyme), secretion of various cytokines (such as IFN-γ and TNF-α), triggering death receptor-mediated apoptosis (such as FasL or TRAIL), ADCC by CD16 antigen expression on the NK cells, and also indirectly via interaction with other immune cells (Cheng et al, 2013). Progression of liver disease led to reduction, functional impairment and exhaustion of NK cells (Cai et al, 2008;Sun et al, 2015), so numerous strategies have been reported to overcome this problem which summarized in our previous study (Hosseinzadeh et al, 2018). One of the problem solving approaches is transplantation of NK cells to HCC patients, but the amount of NK cells derived from various sources is less than clinical use.…”

“…Despite the fundamental role of NK cells in the hepatic regeneration, the frequency and effecter function of NK cells have been impaired over the progression of HCC (Sun et al, 2015). Therefore, there are many strategies to overcome exhaustion or dysfunction of NK cells for HCC treatment (Hosseinzadeh et al, 2018).…”