P- 53 NATURAL KILLER CELLS OF EARLY STAGES OF METABOLIC FATTY LIVER DISEASE PRESENT REDUCED CYTOTOXICITY AGAINST TUMOR CELLS. CASE- CONTROL ANALYSIS

Introduction and Objectives

The liver is considered an important immunological site where natural killer (NK) cells mediate the immune response and tumoral immune surveillance. Understanding the involvement of NK cell function at different stages of metabolic fatty liver disease (MAFLD) is crucial to understand the oncogenic risk of MAFLD and hepatocellular carcinoma (HCC) carcinogenesis. This study aims to characterize the phenotype and function of peripheral NK cells in subjects with different stages of MAFLD.

Materials and Methods

We recruited 15 patients with non-cirrhotic MAFLD (NC-MAFLD), 18 with cirrhosis (CR-MAFLD), and 7 with HCC and compared them with 10 control subjects (HD). Peripheral blood NK cell analysis was performed using multiparametric flow cytometry to characterize NK cells in terms of maturation and function. LDH (lactate dehydrogenase) release assay was used to assess cytotoxicity against tumor cells in isolated NK cells. The results are expressed in percentages in Figure 1 with statistical analysis.

Results

NK cells from patients with NC-MAFLD have a significantly lower cytotoxic capacity than controls (HD=89.7% vs. MAFLD=54.06%, p=0.0115).CD107a, a marker of NK cell degranulation, was significantly reduced in NC-MAFLD and CR-MAFLD after exposure to tumor cells. IFN- (cytotoxicity marker) is reduced in all three MAFLD groups compared to HD. Activation of NKG2D and CXCR3 receptors is significantly decreased in all three MAFLD groups compared to controls, while CD69 is decreased in NC-MAFLD and CR-MAFLD. In addition, the NKG2A (inhibitory receptor) is also decreased (Figure N°1, attached). Markers known to be involved in the NK cell apoptosis process, TRAIL, and FASL, are increased in the cirrhosis and HCC group.

Conclusions

These results suggest that early stages in patients with MASLD (particularly NC-MAFLD) have NK cell dysfunction with reduced cytotoxic capacity and activating receptors. These findings suggest NK cells exhaustion could be present in early stages of MASLD.