Myeloid derived suppressor cells contribute to the malignant progression of oral squamous cell carcinoma
Xin Pang1, Hua-Yang Fan1, Ya-Ling Tang1
1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Purpose:
The 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.
Methods:
Immunochemistry (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.
Results:
The 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.
Conclusion:
These 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.
Insights
Myeloid-derived suppressor cells (MDSCs) fuel oral squamous cell carcinoma (OSCC) progression by promoting proliferation, invasion, and immune suppression. Targeting this crosstalk offers new therapeutic avenues for OSCC treatment.
Area of Science:
- Oncology
- Immunology
- Oral Pathology
Background:
- Myeloid-derived suppressor cells (MDSCs) are key immunosuppressive cells within the tumor microenvironment.
- MDSCs significantly influence cancer progression and patient prognosis.
Purpose of the Study:
- To investigate the interaction between MDSCs and oral squamous cell carcinoma (OSCC) cells.
- To elucidate the role of this crosstalk in OSCC malignant progression and immune suppression.
Main Methods:
- Immunohistochemistry (IHC) for CD33 expression in OSCC tissues.
- Magnetic-activated cell sorting (MACS) for MDSC enrichment and flow cytometry for phenotype identification.
- Co-culture systems of MDSCs and OSCC cells to assess proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry (VM).
Main Results:
- Increased MDSC numbers in OSCC tissues correlated with advanced tumor stage, grade, metastasis, and poor prognosis.
- MDSCs enhanced OSCC proliferation, migration, invasion, EMT, and VM formation in co-culture models.
- OSCC cells induced MDSC differentiation from peripheral blood mononuclear cells (PBMCs) and increased Arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression.
Conclusions:
- The crosstalk between MDSCs and OSCC cells promotes tumor malignancy and immune suppression.
- Targeting tumor-associated immunosuppressive cells like MDSCs presents a promising therapeutic strategy for OSCC.
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