Expression And Clinical Significance Of GARP In Regulatory T Cells Of Lung Cancer Patients

Objective: Recently, it was reported that Glycoprotein A Repetitions Predominant(GARP) was expressed on the surface of regulatory T cells(Tregs). GARP is reguarded as a specific marker of activated Tregs. This study aimed to analyze the expression and clinical significance of GARP in Tregs of lung cancer patients.Methods: Tumor tissue from 39 cases and peripheral blood from 50 cases of lung cancer patients were obtained. We analyzed the expression of GARP on Tregs and conventional T cells(Tconvs) using flow cytometry. The relationship between Tregs or GARP+Tregs and clinicopathological features was analyzed. Tregs cells from lung cancer patients were co-cultured with human lung cancer cells lines A549, H520, H460, LTEP-A-2 and GLC-82 directly or by transwell. The expression of GARP on Tregs was detected in co-culture group, Transwell co-culture group. The effects of supernatant of lung cancer cells on GARP expression of Tregs were also tested.Results: In tumor tissues of lung cancer, Tregs expressed significantly higher levels of GARP than Tconvs(P<0.0001). The proportion of Tregs in tumor tissues was higher than in peripheral blood(P=0.0032). The proportion of GARP+Tregs in tumor tissues was obviously higher than in peripheral blood(P<0.0001). The percentage of GARP+Tregs in tumor tissues of patients with lymph node metastasis was decreased(P=0.0221). Patients with stage III and IV had lower percent of GARP+Tregs(P=0.0005) than patients with stage I and II(P=0.0005). Human lung cancer cells lines A549, H520, H460, LTEP-A-2 and GLC-82 were able to induce the expression of GARP on Tregs. A549 and H520 cells induced much higher levels of GARP than other cells. The expression of GARP in Transwell co-culture group was similar to co-culture group. Besides, the supernatant of lung cancer cells also induced the expression of GARP in Tregs.Conclusion: In tumor tissues of patients with lung cancer, GARP expression was increased in Tregs and associated with lymph node metastasis and clinical stage. Lung cancer cells may induced the expression of GARP in Tregs by secreting certain cytokines.