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Differential Expression Analysis of Natural Killer (NK) Cell Receptor (NKG2D) in Hepatitis C Virus-Infected Chronic Hepatitis and Hepatocellular Patients for the Development of Targeted Immunotherapy

Roya Rozati, Vikram Aiman Ayapati, Gautam Mehdi Ayapati, Aleem Ahmed Khan

Background: Hepatitis C Virus (HCV) infection causes liver cell injury and ultimately results in liver cirrhosis, fibrosis, and further HCC. Despite current treatment strategies using Direct-Acting Anti-virals (DAAs) to treat HCV patients 40% of HCV infection leads to the development of HCC. The Natural killer cells have a crucial role in an immune response against malignant transformation, including hepatocellular carcinoma. As Natural Killer (NK) cells constitute 25%-50% of liver lymphocytes, they have a significant role to play in liver immunity. A positive correlation exists between the number of Natural Killer (NK) cells in the blood and tumor tissues of HCC patients and their survival and prognosis. The NKG2D receptor has a critical role in the Natural Killer (NK) recognition of target cells. Among different mechanisms, Natural Killer (NK) cell-based innate immune response plays a crucial role in the impairment of adaptive immunity post-HCV infection. Natural Killer (NK) cells kill the virus-infected cells through cytolysis, which requires direct contact of Natural Killer (NK) cells with the target cell, and immunological synapse formation. NKG2D is an important Natural Killer (NK) cell receptor, which is activated upon HCV infection resulting in increased cytotoxicity of Natural Killer (NK) cells. Thus, Natural Killer (NK) cells distinguish between normal cells and virus-infected cells through the interaction of NKG2D with its ligands on virus- infected cells. Therefore, Natural Killer (NK) cells are known to contribute to the control of HCV infection itself and have anti-cancer effector functions. Natural Killer (NK) cells being an integral part of the host immune defense against HCV-associated HCC, studying related molecular cascades will provide a newer direction for evolving better predictive biomarkers and designing effective immunotherapeutic strategies.

Methods: A total of 25 HCV infected patients, Chronic HCV (n=15), HCV and HCV related HCC (n=10) and 5 non-infected age and gender matched control subjects were taken in study. Both pre and post-DAA treated patients were included in this study.

Results: The present study has been undertaken to investigate the differential expression analysis of Natural Killer (NK) cell receptors in hepatitis C virus-infected with chronic hepatitis risk of developing HCC.

Conclusion: NKG2D receptor expression and Natural Killer (NK) cell percentage in peripheral blood could provide potential biomarkers for HCC detection and progression.