TIGIT Expression On CD4~+T,CD8~+T And Treg Cells In Peripheral Blood Of Patients With Myelodysplastic Syndromes And The Significance

Background:Myelodysplastic syndrome(MDS)is a highly heterogeneous hematological malignancy with a high risk of transformation to acute myeloid leukemia(AML).There is now considerable evidence that the heterogeneity of the immune micro environment and its interaction with primary cells may be closely related to the development of MDS and the outcome of treatment.As an emerging negatively regulated immune checkpoint,what expression levels and significance the T Cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain(TIGIT)has on the surface of T lymphocyte subsets in MDS patients remains unknown,which is the scientific question of interest in this study.Objective:The study investigated the changes in the expression levels of TIGIT on T-cell subsets including CD4~+T lymphocytes,CD8~+T lymphocytes and regulatory T cells(Tregs)in patients with MDS,and whether they are associated with risk stratifications and immune regulation,trying to provide new ideas for the diagnosis and management of MDS.Methods:21 patients with primary MDS(including 7 in the lower risk group and 14 in the higher risk group),17 healthy controls and 34 controls with primary diagnosis of AML who attended the Department of Hematology of the Second Hospital of Lanzhou University from December 2021 to March 2023 were selected for the study.The expression of TIGIT on CD4~+T,CD8~+T lymphocytes and Tregs in the peripheral blood(PB)was detected by flow cytometry,and the expression levels of serum interleukin 2(IL-2),tumor necrosis factorα(TNF-α),interferonγ(IFN-γ)and IFN-αwere detected by cytometric bead array.The expression levels of TIGIT on each T lymphocyte subpopulation and the relationship with the above cytokines were analyzed by SPSS 27.0.Results:1.The expression levels of TIGIT on CD4~+T lymphocytes and Tregs were upregulated in PB of Lower Risk(LR)MDS patients compared to healthy controls(P<0.001)and downregulated compared to Higher Risk(HR)MDS patients(P<0.05),with no significant correlation with IL-2,TNF-α,IFN-γand IFN-αcytokines.2.The expression levels of TIGIT on CD4~+T lymphocytes,CD8~+T lymphocytes and Tregs were significantly upregulated in HR-MDS patients compared to both healthy controls and AML control group(P<0.001).Correlation analysis showed that TIGIT expression levels on CD8~+T lymphocytes were negatively correlated with IL-2 and IFN-αexpression(P<0.01),and TIGIT expression levels on Tregs were negatively correlated with TNF-αand IFN-γexpression(P<0.05).3.The expression levels of TIGIT on CD4~+T,CD8~+T and Tregs in peripheral blood(PB)of AML control group were negatively correlated with IFN-γexpression(P<0.05).TIGIT levels on Tregs cells were also negatively correlated with IL-2(P<0.01),TNF-α(P<0.05)and IFN-α(P<0.05)expression.Conclusion:1.TIGIT was differentially expressed in LR-MDS,HR-MDS and AML,and also correlated with the expression levels of cytokines,which suggests that TIGIT and relevant cytokines may be involved in the development of MDS and the disturbance of the immune microenvironment.2.Targeted strategies for TIGIT are expected to be a new therapeutic approach for MDS.