Objective: To explore the possible mechanism of lentinan in improving the immune function of patients with advanced NSCLC through a variety of pathways related to lung cancer immunity, and to provide a theoretical basis for the improvement of immunity of lentinan and its anti-tumor effect. Methods: The subjects were the same as the Part Ⅰ. The fasting venous blood was taken before and after treatment. The PBMNCs were obtained after PBMNC separation, centrifugation and washing. The expression levels of PD-1 protein, PD-L1 protein, Jak2 protein, Jak3 protein, Stat3 protein, P13K protein, p-AKT protein in PBMNCs were detected by Western blot. The expression levels of PD-1 mRNA, PD-L1 mRNA, Jak2 mRNA, Jak3 mRNA, Stat3 mRNA, P13K mRNA, p-AKT mRNA in PBMNCs were detected by Real-time quantitative PCR. Results: In the PD-1/PD-L1 signaling pathway, the levels of PD-1 protein, PD-1 mRNA, PD-L1 protein and PD-L1 mRNA in PBMNC were significantly lower after treatment (P<0.05). The levels of PD-1 protein, PD-1 mRNA, PD-L1 protein and PD-L1 mRNA in the treatment group were lower than those in the control group. The difference of PD-1 protein, PD-1 mRNA, PD-L1 protein and PD-L1 mRNA before and after treatment was higher than that of the control group. (P<0.05).In JAK/STAT signaling pathway, the levels of Jak2 protein, Jak2 mRNA, Jak3 protein, Jak3 mRNA, Stat3 protein and Stat3 mRNA in PBMNC were significantly lower than those before treatment (P<0.05). Comparison between groups showed combination therapy. The levels of Jak2 protein, Jak2 mRNA, Jak3 protein, Jak3 mRNA, Stat3 protein and Stat3 mRNA in PBMNC group were lower than those in control group. The difference between Jak2 protein, Jak2 mRNA, Jak3 protein, Jak3 mRNA, Stat3 protein and Stat3 mRNA before and after treatment was higher than that of control. Group (P < 0.05).In the PI3K-AKT signaling pathway, the levels of P13K protein, P13K mRNA, p-AKT protein, p-AKT mRNA in PBMNC were significantly lower than those before treatment (P<0.05). The comparison between groups showed that the levels of P13K protein, P13K mRNA, p-AKT protein, p-AKT mRNA in PBMNC of the combined treatment group were lower than those of the control group, P13K protein, P13K mRNA, p-AKT protein, p- The difference of AKT mRNA levels before and after treatment was higher than that of the control group (P<0.05). Conclusion: Lentinan may improve the immunity of NSCLC patients through PD-1/PD-L1 signaling pathway, JAK/STAT signaling pathway and PI3K-AKT signaling pathway.
