DISCUSSION
Lung cancer is the leading cause of cancer-related death worldwide. As the main histological subtype of lung cancer, NSCLC attracts a lot of attention. In the past 20 years, advantages in the treatment of NSCLC have been achieved tremendously, and the understanding for NSCLC biology and progression has also been more comprehensive [8]. For instance, applications of small molecule tyrosine kinase inhibitors and immunotherapy have resulted in unprecedented survival benefits in selected patients [30-33]. However, the overall cure and survival rates of NSCLC patients still remain at a low rate, especially in metastatic condition [8]. MDSCs that are a population of IMCs with immunosuppression are a major cause of NSCLC immune escape, metastasis and therapy resistance [34-37]. As the major population of MDSCs, PMN-MDSCs account for 70-80% of total MDSCs in both tumor-bearing mice and cancer patients. PMN-MDSCs suppress anti-tumor immune responses by releasing high levels of arginase 1 (ARG1) and reactive oxygen species (ROS) [38]. The phenotype of PMN-MDSCs is complicated. PMN-MDSCs were previously characterized as CD11b+Ly6G+Ly6Clowin mice, and were identified as CD11b+CD33+CD15+CD66b+CD14-in human, which shared the same phenotype with mature neutrophils [15]. LOX-1 is a newly defined marker that can distinguish human PMN-MDSCs from mature neutrophils, and peripheral LOX-1+ PMN-MDSCs is associated with anti-PD-1 therapy in NSCLC patients [27]. Here, we demonstrated that CD15+LOX-1+ PMN-MDSC proportion increased in PB of NSCLC patients. The frequency of circulating CD15+LOX-1+ PMN-MDSCs was positively correlated with the levels of CEA and CYFRA21-1, and the combined detection of PMN-MDSCs and traditional tumor markers could enhance the diagnostic sensitivity and specificity for NSCLC. Moreover, we found that the proportion of CD15+LOX-1+PMN-MDSCs in PB of NSCLC patients decreased at one month after surgical resection, indicating that CD15+LOX-1+ PMN-MDSCs are associated with the prognosis of NSCLC. NSCLC recurrence after surgery is responsible for cancer associated mortalities after resection. To confirm the relationship between CD15+LOX-1+ PMN-MDSCs and NSCLC recurrence, we detected the PMN-MDSC frequency in NSCLC patients with or without recurrence after resection, and it was found that PMN-MDSC percentage was much higher in patients with recurrence. Therefore, CD15+LOX-1+ PMN-MDSCs are associated with NSCLC recurrence after surgery. However, PB samples in this study were all from primary NSCLC patients in early stage that were diagnosed for the first time and had not received any treatment before. CD15+LOX-1+ PMN-MDSC presence in the circulation of III-IV NSCLC patients have not been revealed. Besides that, we only measured the frequency of CD15+LOX-1+ PMN-MDSCs before/after surgical treatment, but the relationship between CD15+LOX-1+ PMN-MDSCs and other treatments, such as radiotherapy, chemotherapy and targeted therapy, still needs further investigations.