Objective:To investigate whether lung cancer cells can directly influence the methylation of IFN-γ gene promoter in CD4+T cells. Methods:The plasma level of IFN-γ was determined by ELISA in the lung cancer patient group (n = 30) and healthy control group(n = 30). CD4+T cells were isolated by CD4-positive isolation kit from peripheral blood of lung cancer patients (n = 8) and healthy controls (n = 8),and genomic DNA was extracted using QIAamp Mini Kit and bisulfite treated. IFN-γ gene promoter methylation was analyzed with methylation specific sequencing method and the result was analyzed by bioinformatics software;A Transwell culturing system was also established (n = 6). CD4+ T cells of healthy volunteers were co-cultured with SPC-A1 as the experimental group and CD4+ T cells cultured as the control group. After culturing for 5 d,CD4+ T cells were collected to analyze IFN-γ gene promoter methylation using methylation specific sequencing method as described above. Meanwhile,CD4+ T cells were stimulated by anti-CD3 and anti-CD28 antibodies for 6 and 24 h. The IFN-γ of supernatant was detected by ELISA and RT-PCR was used to determine the mRNA transcript levels of IFN-γ. Results:The level of plasma IFN-γ was significantly lower in lung cancer patients (69.30 ± 38.56 pg/ml vs 92.62 ± 34.75 pg/ml,P = 0.017). The hypermethylation status of IFN-γ promoter in CD4+ T cells of lung cancer patients was 84.6%(control,68.6%)(P < 0.001). The concentration of plasma IFN-γ was negatively correlated with the percentage of methylation at the IFN-γ promoter in the patient group(r = -0.850 3,P = 0.010 7). In Transwell culturing system,after stimulation for 6 and 24 h,the expression of IFN-γ in the experimental group was significantly lower than that of the control group [6 h:(14.53 ± 7.12) pg/ml vs (36.14 ± 23.51) pg/ml,24 h:(7.81 ± 4.02) pg/ml vs (24.85 ± 15.58) pg/ml]. The mRNA transcript levels of IFN-γ of the control groups were increased 2.37 fold after stimulation for 6 h. The hypermethylation status of the IFN-γ promoter in CD4+ T cells of the experimental group was 85.4%(control,70.9%). Conclusion:Lung cancer cell can induce the hypermethylation of IFN-γ gene promoter,which downregulates the expression of the IFN-γ gene,and it may play an important role on the immunosuppression of lung cancer patients.