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.