The Dynamic Role of NK Cells in Liver Cancers: Role in HCC and HBV Associated HCC and Its Therapeutic Implications

Abstract

Hepatocellular carcinoma (HCC) remains an important complication of chronic liver disease, especially when cirrhosis occurs. Existing treatment strategies include surgery, loco-regional techniques, and chemotherapy. Natural killer cells are distinctive cytotoxic lymphocytes that play a vital role in fighting tumors and infections. As an important constituent of the innate immune system against cancer, phenotypic and functional deviations of NK cells have been demonstrated in HCC patients who also exhibit perturbation of the NK-activating receptor/ligand axis. The rate of recurrence of tumor-infiltrating and circulating NK cells are positively associated with survival benefits in HCC and have prognostic significance, suggesting that NK cell dysfunction is closely related to HCC progression. NK cells are the first-line effector cells of viral hepatitis and play a significant role by directly clearing virus-infected cells or by activating antigen-specific T cells by producing IFN-γ. In addition, chimeric antigen receptor (CAR) engineered NK cells suggest an exclusive opportunity to produce CAR-NKs with several specificities with fewer side effects. In the present review, we comprehensively discuss the innate immune landscape of the liver, particularly NK cells, and the impact of tumor immune microenvironment (TIME) on the function of NK cells and the biological function of HCC. Furthermore, the role of NK cells in HCC and HBV-induced HCC has also been comprehensively elaborated. We also elaborate on available NK cell-based immunotherapeutic approaches in HCC treatment and summarize current advancements in the treatment of HCC. This review will facilitate researchers to understand the importance of the innate immune landscape of NK cells and lead to devising innovative immunotherapeutic strategies for the systematic treatment of HCC.

Biomaterial-Mediated Exogenous Facile Coating of Natural Killer Cells for Enhancing Anticancer Efficacy toward Hepatocellular Carcinoma

“…The one −COOH group of TBA was conjugated with DSPE PEG -NH 2 and another two − COOH groups were conjugated with PEG (Figure 1). In this 1 H NMR peaks with respect to the core phenyl protons at δ8.47 ppm. The terminal CH 3 group of DSPE PEG at δ0.85 ppm was integrated with respect to the phenyl ring of core benzoic acid at δ8.47 ppm (3H).…”

“…Liver cancer, which is an invasive tumor, is a common cancer in patients with a history of hepatitis or cirrhosis. It is the fourth leading cause of cancer-related death worldwide due to its increasing morbidity and high malignancy . In particular, hepatocellular carcinoma (HCC) is the most common type of liver cancer, found in more than 90% of liver cancer patients .…”

“…It is the fourth leading cause of cancer-related death worldwide due to its increasing morbidity and high malignancy. 1 In particular, hepatocellular carcinoma (HCC) is the most common type of liver cancer, found in more than 90% of liver cancer patients. 2 Although many researchers have attempted to find HCC treatments including tumor ablation, transarterial chemoembolization, and chemotherapy, the current treatments are still less effective and have low patient survival rates.…”

Application of adoptive cell therapy in hepatocellular carcinoma

“…Adoptive immunotherapy is a promising therapeutic approach to target infections, autoimmune diseases and malignancies by infusing in vitro activated and expanded autologous or allogeneic immune effector cells into patients. In recent years, cellular immunotherapy has been widely used as a novel therapeutic modality for tumour treatment and has achieved positive clinical results [17][18][19][20]. At present, adoptive immunotherapy is mainly for patients with advanced hepatocellular carcinoma after failure of surgical resection, local or systemic therapy.…”

Combined analysis of bulk and single-cell RNA sequencing reveals novel natural killer cell-related prognostic biomarkers for predicting immunotherapeutic response in hepatocellular carcinoma

“…The importance of innate immune cells has not gotten enough attention in the contemporary setting of antitumor immunity, which has mostly focused on adaptive T-cell responses, like CD4+ CD25+ Foxp3 regulatory T cells (Tregs), cytotoxic T lymphocytes (CTLs) et all ( 3 , 4 ). By specifically identifying and eliminating tumor cells and encouraging adaptive T-cell immunity responses, natural killer (NK) cells are a subtype of innate immune cells that can reduce the proliferative and invasive potential of tumor cells at an early tumor stage ( 5 ). The balance of inhibitory and activating receptors that can interact with ligands on target cells determines how well NK cell function.…”