Abstract
PurposeThe tumor-related myeloid derived suppressor cells (MDSCs), important immunosuppressive cells in tumor microenvironment, play an important role in the cancer progression. This study is aimed to investigate the crosstalk between MDSCs and oral squamous cell carcinoma (OSCC) cells and their role in the malignant progression of OSCC.MethodsImmunochemistry (IHC) was used to investigate the expression of CD33 in 200 OSCC, 36 premalignant. CD33+ MDSCs were sorted and enriched via magnetic-activated cell sorting (MACS) from OSCC patients or health donor, and their phenotypes were identified by flow cytometry. With a co-culture system of MDSCs and OSCC, the effects of MDSCs on OSCC proliferation, apoptosis, migration invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry formation (VM) formation were assessed, respectively. Besides, peripheral blood mononuclear cells (PBMCs) from health donor were cultured with OSCC supernatant, the level of MDSCs and expressions of Arginase (Arg-1) and inducible nitric oxide synthase (iNOS) were measured.ResultsThe number of MDSCs was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis. Tumor-related MDSCs of the co-culture system promoted OSCC progression by contributing to cell proliferation, migration and invasion as well as inducing EMT and VM. In turn, OSCC cells had potential to induce MDSCs differentiation from PBMCs and increase the expression of Arg-1 and iNOS.ConclusionThese indicated that the crosstalk between MDSCs and tumor cells facilitated the malignant progression of OSCC cells and the immune suppressive properties of MDSCs, which may provide new insights into tumor treatment on targeting tumor-associated immunosuppressive cells.
Highlights
Oral squamous cell carcinoma (OSCC), whose risk factors include alcohol use, tobacco exposure, continued stimulation, and virus infection, is the most common malignancy among oral cancers [1,2,3]
The number of myeloid derived suppressor cells (MDSCs) was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis
To determine the role of MDSCs in OSCC, a total of 200 OSCC patients (143 men and women; mean age, [19–84] years) and 36 premalignant lesions (27 men and 9 women; mean age, 54 [14–65] years) were collected to perform IHC to analysis the expression of CD33
Summary
Oral squamous cell carcinoma (OSCC), whose risk factors include alcohol use, tobacco exposure, continued stimulation (areca chewing, for instance), and virus infection, is the most common malignancy among oral cancers [1,2,3]. Identifying new therapeutic targets to inhibit the malignant progression and improve the overall survival (OS) of OSCC patients is in the Spot-LIGHT of researches. Immune microenvironment consists of a variety of immune cells which can cooperate with each other to inhibit or in contrast be subverted to promote growth and progression of tumor [8, 9]. Among these inmmune cells, myeloid derived suppressor cells (MDSCs), first identified as natural suppressor cells in 1984, which are a heterogeneous group of immature dendritic cells, granulocytes, macrophages, and bone marrow precursor cells, mainly create an immunosuppressive microenvironment [10]. Several studies have shown that MDSCs levels are positively related to histological differentiation, nodal metastasis, and recurrence of OSCC patients [20], the role and mechanism of MDSCs in the malignant progression of OSCC is still unclear
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