Expression Of Negative Costimulatory Molecule TIM-3on Non-small Cell Lung Caner T Cell And MDSCs And Its Significance

Tumor is a kind of ecosystem consisting of tumor cells, infiltration of immune cellsand stromal cells and the a series of molecules in microenvironment. Infiltratingimmune cells in the tumor microenvironment is one of the important factors for thedevelopment of tumors. infiltration of immune cells including effector T cells,regulatory T cells, anergic T cells, exhausted T cells, macrophages, granulocytes andmyeloid-derived suppressor cells (MDSC) in the tumor microenvironment play adifferent role and affect the whole process of tumor progression.In-depth study of the tumor microenvironment and tumor immune escapemechanisms in recent years, a group of negative costimulatory molecules mediatingimmune regulation were found and were called immune checkpoints, such as negativeB7family molecules, CTLA-4, TIM-3and so on. Those molecules abnormallyexpressed on a range of tumor tissue and/or infiltrating immune cells involving intumor immune escape, and closely related with clinical pathology and prognosis,constitute an important component of the tumor microenvironment.TIM-3, a number of the TIM family(T cell immunoglobulin andmucin-domain-containing molecules), mainly expressed on the differentiated Th1cellsand cytotoxic CD8+T cells, monocytes, cells, dendritic cells, is also considered to be animportant marker of the CD8+T cell exhaustion/anergy, and its role in tumor immunityis getting more and more attention.In different stages of tumor development, infiltrating T lymphocyte subsets andinhibitory immune cells (such as MDSC) in tumor microenvironment by expressingimmune checkpoints mediate anti-tumor immune response and tumor immune escape.The deeply research of expression characteristics of negative costimulatory moleculeTIM-3on infiltrating T lymphocyte subsets and myeloid-derived suppressor cells, therelevance to clinical factor and their participation in tumor immune escape mechanismcan provide a new theoretical basis and target for tumor immunotherapy based onintervention TIM-3signaling pathways. Objective: To explore the expression and clinical significance of negativecostimulatory molecules TIM-3on non-small cell lung cancer T cells andmyeloid-derived suppressor cells.Methods: Obtain cancer tissues and adjacent cancer tissues surgical removed from51non-small cell lung cancer (NSCLC) patients. By digesting and mechanicalpulverizing obtain a single cell suspension. Using lymphocyte separation medium getmononuclear cells.By immunofluorescence and flow cytometry detect TIM-3’sexpression on tumor-infiltrating T lymphocytes and MDSC. At the same time collectedthe same patients and healthy volunteers’ peripheral blood.Byimmunofluorescence,hemolysis and flow cytometry detect TIM-3’s expression onperipheral blood T lymphocytes and MDSC. Analysis the relevance between TIM-3’sexpression on non-small cell lung cancer patients’ T-cell and clinicopathological factors.Results:(1) Compared to adjacent normal tissue-infiltrating lymphocytes andperipheral blood T cells, expression of TIM-3were significantly increased on tumortissue TILs surface in patients with non-small cell lung cancer;(2) Statistical analysisshowed that the expression of TIM-3molecules on tumor-infiltrating CD4+Tlymphocytesin patients with NSCLC is correlated with lymph node metastasis and stage;(3) Compared to healthy controls,MDSC in peripheral blood of patients with non-smallcell lung cancer highly expressed negative costimulatory molecule TIM-3; Comparedto adjacent tissues, expression of TIM-3was also significantly up-regulated in thetumor tissue of the same patient.Conclusion: TIM-3on tumor infiltrating CD4+and CD8+T lymphocytesin inpatients with non-small cell lung cancer have high expression and TIM-3on tumorinfiltrating CD4+T cells in non-small cell lung cancer is correlated with tumor lymphnode metastasis and patient’s pathological stage.MDSC in peripheral blood and tumortissue of patients with non-small cell lung cancer highly expressed negativecostimulatory molecule TIM-3.The results obtained provide new ideas and mechanismsto further explore the negative regulatory role of TIM-3molecules in the tumormicroenvironment.