Expression Of PD-1,TIM-3 And LAG-3 In T Lymphocytes From Acute Leukemia Patients Underwent Allogeneic Hematopoietic Stem Cell Transplantation And Their Potential Clinical Implications

Objective:PD-1,TIM-3,and LAG-3 are negative co-stimulatory molecules involved in the immune escape mechanism of tumor cells.This study analyzed PD-1,TIM-3,and LAG-3 expression feature in T lymphocytes from acute leukemia patients after allogeneic hematopoietic stem cell transplantation.Methods:PD-1,TIM-3,LAG-3 expression levels in CD4~+,CD8~+,CD3~+ T lymphocyte from peripheral blood were test by flow cytometry in 23 healthy volunteers(Healthy control group)and 36 patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)in 1 month,2 months,3 months,4.5 months and 6 months.Statistical analysis of PD-1,TIM-3,and LAG-3 expression levels in transplant patients and healthy control group.Then,patients were grouped according to whether Minimal residual disease was positive after transplantation,whether to use Donor lymphocyte infusions,whether Graft-versus-host disease was positive,whether hormones were used,whether were infected by CMV、EBV、BKV or JCV.After that,we collected the clinical data of the transplant patient group,and analyzed the differences between these groups in the expression levels of PD-1,TIM-3,and LAG-3 in peripheral blood T lymphocytes and summarized their expression characteristics and clinical significance.Results:1.The expression levels of PD-1 and TIM-3 in T lymphocytes of acute leukemia patients at early stage after allo-HSCT were higher than normal levels and showed a decreasing trend with time.The expression levels of LAG-3 in CD8~+ T lymphocytes were lower in the transplant patient group than in the healthy control group at each detection time point(all P <0.05).2.PD-1’s expression level in T lymphocytes of one acute leukemia patients post allo-HSCT increased at 3 months before relapse.This may indicate disease relapse.3.The expression levels of PD-1 in CD4~+,CD8~+ T cells and TIM-3 and LAG-3 in T cells of acute leukemia patients post allo-HSCT in early GVHD group were not significantly different from those in n GVHD group.4.The expression levels of PD-1,TIM-3,and LAG-3 in T lymphocytes of two acute leukemia patients after DLI showed a downward trend compared with those before treatment.One patient’s expression levels of PD-1 in T lymphocytes decreased at 3 months after DLI.So did TIM-3’s expression levels in CD3~+CD4~+ T lymphocytes.5.The expression levels of PD-1 in CD3~+CD4~+ T lymphocytes and TIM-3 in CD4~+,CD8~+,CD3~+ T lymphocytes in virus group were higher than those in virus-negative group(all P <0.05).The expression levels of PD-1 of the CMV group were higher than those in the non-CMV group(all P <0.05);the expression levels of PD-1 of the BKV group were higher than those in the non-BKV group(all P <0.05),and the levels were not related to the length of virus infection.6.The expression levels of PD-1 in CD4~+,CD8~+,and CD3~+ T lymphocytes in the hormone group were higher than that in the non-hormonal group at 1 month after transplantation(all P <0.05).Conclusion:1.The expression levels of PD-1 and TIM-3 in T lymphocytes of acute leukemia patients at early stage after allo-HSCT are higher than normal levels and show a decreasing trend with time.The expression levels of LAG-3 in the transplantation patient group at each test time point are lower than that in the healthy control group.2.a GVHD has no obvious effect on the expression of PD-1,TIM-3 and LAG-3 in T lymphocytes of acute leukemia patients post allo-HSCT.3.DLI can reduce PD-1,TIM-3 positive ratio in T lymphocytes of acute leukemia patients post allo-HSCT.4.PD-1’s expression levels in T lymphocytes increases during viral infection in acute leukemia patients post allo-HSCT.