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.
Moreover, NSCLC can be subdivided into squamous cell carcinoma,
adenocarcinoma and large cell carcinoma [3-5]. In spite of the
development in lung cancer treatment, such as surgery combined with
radiotherapy, chemotherapy, and immunotherapies, NSCLC recurrence after
surgery still remains at a high rate [6-8]. Cancer metastasis is
identified as the main cause of 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 [9-11]. Immune
checkpoint blockade that can promote the generation of antigen specific
T cells is a newly defined immune adjuvant therapy [12, 13].
However, most of early-stage NSCLC tumors are removed without the
absence of neoadjuvant intervention in clinical practice [10, 14].
Therefore, novel strategies are necessary for monitoring and decreasing
the recurrence and metastasis in patients with primary 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 [15-18]. 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. One of the immuosuppressive
populations that are rapidly attracting attention in tumor biology is
MDSCs [19]. MDSCs are a population of immature myeloid cells (IMCs)
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 [20-22]. 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 [23]. PMN-MDSCs have been confirmed to be
involved in the progression of NSCLC by promoting tumor immune escape
and metastasis in both preclinical and clinical trails [24-26].
However, PMN-MDSCs were initially identified as a population of
terminally differentiated neutrophils with immunosuppression, which
shared 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 [19]. Recently,
it was confirmed that LOX-1 could be used to distinguish the population
of PMN-MDSCs in cancer patients [27-29]. Thus, in present study, we
tried to ensure the application of newly defined
CD15+LOX-1+ PMN-MDSCs in NSCLC
diagnosis and prognosis, as well as identify their association with
NSCLC recurrence after surgery.