The role of natural killer cells in hepatocellular carcinoma development and treatment: A narrative review

Abstract

A major obstacle for treatment of HCC is the inadequate efficacy and limitation of the available therapeutic options. Despite the recent advances in developing novel treatment options, HCC still remains one of the major causes of cancer morbidity and mortality around the world. Achieving effective treatment and eradication of HCC is a challenging task, however recent studies have shown that targeting Natural Killer cells, as major regulators of immune system, can help with the complete treatment of HCC, restoration of normal liver function and subsequently higher survival rate of HCC patients. Studies have shown that decrease in the frequency of NK cells, their dysfunction due to several factors such as dysregulation of receptors and their ligands, and imbalance of different types of inhibitory and stimulating microRNA expression is associated with higher rate of HCC progression and development, and poor survival outcome. Here in our review, we mainly focused on the importance of NK cells in HCC development and treatment.

Association Between Circulating Lymphocyte Populations and Outcome After Stereotactic Body Radiation Therapy in Patients With Hepatocellular Carcinoma

“…The counts of peripheral NK cells in patients with better survival remained significantly elevated compared to those in short-term survivors at 10 days to 2 months after SBRT ( p < 0.05). NK cells, which are innate lymphoid cells with natural cytotoxicity and regulatory functions, play an integral role in the immune defense mechanism against malignant tumors such as HCC (38, 39). NK cells account for 25–50% of the total number of liver lymphocytes, suggesting their important role in liver immunity (40).…”

“…NK cells account for 25–50% of the total number of liver lymphocytes, suggesting their important role in liver immunity (40). The number of NK cells in both blood and tumor tissues of HCC patients is positively correlated with patient survival (39). Hence, these findings rationalized the significant association between SBRT-induced NK cell loss and inferior survival in HCC patients.…”

Regulatory T cell and activated natural killer cell infiltration in hepatocellular carcinoma: immune cell profiling using the CIBERSORT

“…NK cell regulation of antigen-specific T lymphocytes occurs during viral infection. When NK cells become depleted, the number of antigen-specific T lymphocytes increases; therefore, these NK cells may reduce T cell levels, leading to a weaker antitumor immune response (50). NK cell activator has been shown to induce liver inflammation by significantly increasing the levels of infiltrating lymphocytes, along with concurrently increasing apoptosis and proliferation of hepatocytes; consequently, epithelial-to-mesenchymal transition of hepatocytes is accelerated (51).…”

Immunological characterization of hepatocellular carcinoma

“…Indeed, a greater proportion of NK cells in the tumor microenvironment is correlated with improved survival among HCC patients [17] . Conversely, reduced NK cell frequency and activity are associated with HCC progression [20] . Impaired NK cell function is found in cirrhosis and HCC.…”