INTRODUCTION
Lung cancer has become a challenging health problem worldwide. More than 1.0 million people die of the disease each year [1, 2]. According to the histopathological classification, lung cancer can be divided into small cell lung cancer (SCLC) and NSCLC, in which NSCLC accounts for approximately 85% and is the most common type of clinical lung cancer. NSCLC can be subdivided into squamous cell carcinoma, adenocarcinoma and large cell carcinoma [3-5]. In spite of the development in lung cancer diagnosis and treatment, the overall survival of NSCLC still remains at a low rate [6-9]. Metastasis is identified as the main cause of lung cancer related mortalities after resection. It is confirmed that 30-55% of NSCLC patients in early stage die from recurrent metastatic disease after surgery with curative intent, and only 3-10% of them can survive over 5 years with the treatment of standard adjuvant chemotherapy [10-12]. Immune checkpoint blockade that can promote the generation of antigen specific T cells is a newly defined immune adjuvant therapy [13, 14]. However, most of early-stage NSCLC tumors are removed without neoadjuvant intervention in clinical practice [11, 15]. Current biomarkers for NSCLC such as CYFRA21-1, CEA and CA125 are not specific and sensitive enough to reflect the NSCLC progression. Therefore, specific biomarkers are necessary for monitoring NSCLC development and developing targeted treatment approaches for NSCLC.
In the progression of lung cancer, there exist multiple immune cells infiltrating into tumor sites. Different types of these immune cells and their products determine the fate of tumor progression. Immune cells also play a major role in establishing metastasis of the primary tumor to various organs [16-19]. A protective immune response against tumor is often prevailed by the protumor response, and it eventually is the balance or the lack of it between these two processes that determine the fate of tumor growth and metastasis. MDSCs are one of the immuosuppressive populations, which are rapidly attracting attention in tumor biology [20]. MDSCs are a population of immature myeloid cells (IMCs) and mature myeloid cells with immune suppressive activity. Under physiological conditions, IMCs produced by bone marrow can differentiate into mature granulocytes, monocytes and dendritic cells (DCs). In pathological conditions, especially cancer, the differentiation of IMCs is inhibited by molecules released by tumor cells, stromal cells and activated immune cells, which leads to the accumulation of MDSCs [21-23]. In human and mice, PMN-MDSCs and monocytic MDSCs (M-MDSCs) are the two main subsets of MDSCs, in which PMN-MDSCs that account for 70-80% of total MDSCs are the prioritized population [24]. In tumor microenvironment (TME), PMN-MDSCs are the main subset of MDSCs that induce tumor immune escape. Besides PMN-MDSCs migrating from bone marrow to TME, M-MDSCs and mature granulocytes in TME can also convert into PMN-MDSCs to induce the immunosuppression more effectively [25]. PMN-MDSCs have previously been confirmed to be involved in the progression of NSCLC by promoting tumor immune escape and metastasis in both preclinical and clinical trails [26-28]. However, PMN-MDSCs, which were initially identified as a population of terminally differentiated neutrophils with immunosuppression, shared the similar morphology and phenotype with mature ones. Therefore, it was the suppressive activity, but not phenotype, was the most reliable approach to distinguish PMN-MDSCs from neutrophils [20]. Recently, it was confirmed that LOX-1 could be used to distinguish the population of PMN-MDSCs in cancer patients. It was found that the newly defined LOX-1+CD15+ PMN-MDSCs enhanced immune suppression which promoted tumor progression [29-32]. Thus, we attempted to ensure the application of CD15+LOX-1+ PMN-MDSCs in NSCLC diagnosis in present study, as well as identify their association with NSCLC prognosis and recurrence after surgery.