Lee, H.G. and recurrence risk of HCC have not been fully evaluated. Methods Untreated individuals with newly diagnosed HCC were prospectively enrolled. Peripheral blood mononuclear cells were isolated at the time of analysis. Individuals who experienced undergone surgery or radiofrequency ablation were classified as the curative treatment group, and their blood samples were collected again at 1?month after treatment. Results A total of 80 individuals with HCC were enrolled. The mean age was 62.5?years. At baseline, interferon (IFN)- generating NK cell proportion was significantly reduced individuals with Barcelona medical center liver tumor (BCLC) stage B, C, or D than in those with BCLC stage 0 (42.9% vs. 56.8%, Barcelona clinic liver cancer, individuals with BCLC stage 0, individuals with BCLC stage A, individuals with BCLC stage B, C, or D producing NK cell proportion significantly decreased in advanced-stage HCCvalueBarcelona clinic liver cancer, interferon NK cell AMD3100 (Plerixafor) profiles were not significantly changed after curative treatment There were no significant Rabbit Polyclonal to PRKCG changes in total NK cell proportion (9.6% vs. 11.2%, producing NK cell AMD3100 (Plerixafor) proportion at 1?month after curative treatment significantly predicted HCC recurrencevaluevaluehepatocellular carcinoma, hazard ratio, confidence interval, Barcelona medical center liver tumor, interferon Discussion Problems in NK cell functions have been suggested while important mechanisms for tumor development [37]. However, the association between NK cell dysfunction and HCC progression and recurrence has not been fully evaluated. Especially, little info is currently available concerning post-treatment NK cell function. AMD3100 (Plerixafor) This prospective study recruited untreated individuals with newly diagnosed HCC, and investigated the medical implication of peripheral blood NK cell activity in HCC stage and recurrence after curative treatment. Our results showed that IFN- generating NK cell proportion significantly decreased in individuals with intermediate and advanced-stage HCC than very early-stage HCC (42.9% vs. 56.8%, em P /em ?=?0.045). Individuals with? ?45% IFN- generating NK cell proportion at 1?month after treatment exhibited a higher incidence of HCC recurrence than individuals with that of ?45% ( em P /em ? ?0.001). Moreover, BCLC stage B or C (HR?=?3.412) and IFN- producing NK cell proportion at 1?month after treatment? ?45% (HR?=?6.934) independently predicted an increased risk of HCC recurrence (all em P /em ? ?0.05). These findings show that NK cell activity decreases in advanced-stage HCC, and individuals with decreased NK cell activity at after curative treatment are at higher risk of HCC recurrence actually after effective treatment. Our study has several advantages and medical implications. First, the association between peripheral blood NK cell activity HCC stage has not been fully clarified in earlier studies [19, 20]. In AMD3100 (Plerixafor) the present study, we observed that, although the total NK cell proportion was rather higher in individuals with BCLC BCD than in those with BCLC A HCC ( em P /em ?=?0.046), the total IFN- producing NK cell proportion was significantly reduced individuals with BCLC BCD than in those with BCLC 0 ( em P /em ?=?0.045), and a tendency of reduce IFN- producing NK cell proportion was observed in individuals with BCLC AMD3100 (Plerixafor) BCD than in those with BCLC A ( em P /em ?=?0.080). These findings show that circulating NK cells shed their capacity to produce IFN- in advanced HCC, hindering anti-tumor immune response in individuals with HCC, and these problems are aggravated with HCC progression regardless of the total NK cell number. It has been well known that NK cells play a major part in initiation and progression of HCC through numerous mechanisms including decreased frequency and defective cytokine secretion [38]. Cai et al. showed related result with peripheral blood (IFN- generating NK cell proportion of healthy settings vs. Chinese classification Stage I, II, or III, all em P /em ? ?0.05) [20]. However, individuals in Chinese classification stage III experienced higher IFN- generating NK cell proportion than those in stage I or II. This disparity may be caused by the difference in HCC staging system. The Chinese classification system was developed in 1999, and not offers been widely used for HCC staging. Second, we found that? ?45% IFN- generating NK cell proportion at 1?month after curative treatment was independently associated with an increased risk of HCC recurrence (HR?=?6.934). Interestingly, the IFN- generating NK cell proportion at diagnosis experienced no significant association with HCC recurrence. This result shows that repair of NK cell activity after successful removal of tumor and related microenvironment may play a more critical part in HCC recurrence than decreased NK cell activity at baseline. Earlier studies possess only evaluated the relationship between NK cell activity at analysis and prognosis of individuals with HCC..