The Regulation And Function Of Programmed Death-1 In T-cell Acute Lymphoblastic Leukemia

PD-1(Programmed cell death-1)is a negative immune checkpoint upregulated in activated human T-cells and T-cell lymphoma cells.Although PD-1 inhibitors have been approved for treatment of several solid tumors and hematological tumors,its expression and roles in tumor cells derived from patients with T-cell acute lymphoblastic leukemia(Patient-derived T-ALL,PDT-ALL)have not been confirmed yet.Therefore,the detection of PD-1 expression and in-depth studies on its molecular mechanism in PDT-ALL cells exhibit certain scientific and clinical significance.The differential expression of immune checkpoints in the peripheral blood CD3+T cells from healthy donors and PDT-ALL cells was analyzed by flow cytometry,and the results were subsequently validated using Q-PCR and RT-PCR.The results confirmed the high expression of PD-1 in PDT-ALL cells.After that,the expression of transcription factors regulating PD-1 expression was determined using Q-PCR,and the data showed that the expressional changes of transcription factors(T-bet,Blimp-1 and NOTCH1)in PDT-ALL cells were associated with the abberant expression of PD-1.Blockade of PD-1 signaling in PDT-ALL cells with the PD-1 blocking antibody was performed in vitro and in vivo,and the consequences showed that PD-1 blocking antibody affected.the expression of IGFBP3 and SULT1A3 in PDT-ALL cells in vitro.Besides,the results of assays in mice showed that the treatment with PD-1 blocking antibody inhibited the proliferation and infiltration of PDT-ALL cells in the spleen,In summary,PD-1 immune checkpoint is highly expressed in PDT-ALL cells,and plays a certain positive role in the initiation and development of T-ALL.Hence,our study has provided a theoretical basis for the administration of PD-1 blocking antibody in the clinical treatment of T-ALL.