The Study Of B7-H1/PD-1 Pathway Inhibitor Enhances Chemotherapeutic Effect Of Cisplatin

[Objective]To explore the anti-tumor effect and the influence of antitumor immunity of B7-H1/PD-1 blocked by PD-1 antibody combined with cisplatin.[Methods](1) Tumor models were established by injecting TC-1 cells into C57BL/6 mice, there were four groups(n=4):the control group, cisplatin group, PD-1 antibody group and PD-1 antibody combined with cisplatin group. Control group was treated with PBS (100μl/mice),once every three days,2 times; cisplatin group was treated with cisplatin (5mg/kg),once every three days,2 times; PD-1 antibody group was treated with PD-1 antibody (100μl/mice), once every three days,3 times; PD-1 antibody combined with cisplatin group were treated with both cisplatin and PD-1 antibody as the same dosage and schedule. (2) The tumor size of mice were checked once every two days. The tumor growth curves and survival curves were drew to observe the anti-tumor effect. (3) The mice were executed when it died or the tumor diameter reached to 2cm. the spleens were removed and the mononuclear lymphocytes were isolated. The number of CD4+CD25+T regulate cells were analyzed by flow cvtometry. The tumor were removed when the mice were executed. Then the B7-H1 and CD8+T cells were analyzed by immunohistochemical method..[Results]:(1). Among the four groups, the anti-tumor effect in cisplatin, PD-1 antibody and PD-1 antibody combined with cisplatin were all higher than that in control group, which was most obvious in combination treatment group (P<0.05).(2).The survival time of mice in cisplatin、PD-1 antibody group and combination treatment group were significantly longer than those in control group, which was most obvious in combination treatment group (P<0.05).(3).The quantity of Treg cells of splenic mononuclear mononuclear lymphocytes were 52.00±%4.32% in combination treatment group, which were 71.50%±4.04% in cisplatin group、69.75%±3.77% in PD-1 antibody group and 87.00%±6.06% in control group. The quantity of Treg cells of in cisplatin group, PD-1 antibody group and combined group were significantly lower than those in control group, which was most obvious in combination treatment group(P<0.05).(4).The expressions of B7-H1 in tumor tissue were brown by immunohistochemistry, mainly located in cell nuclear and cytoplasm.The expressions of B7-H1 in cisplatin increased(P<0.05)、PD-1 antibody group and combination treatment group were significantly decreased than those in control group, the most obvious decrease happened in the combination treatment (P<0.05).(5).CDS+T cells in tumor tissues were brown by immunohistochemistry, mainly located in the cell membrane. compared to control group,The quantity of CD8+T cells in cisplatin decreased(P>0.05). which increased in PD-1 antibody group and combination treatment group, the most obvious increase happened in the combination treatment (P<0.05).[Conclusions] (1). The tumor growth were suppressed and the survival time of mice were prolonged by cisplatin combined with PD-1 antibody which blocked the B7-H1/PD-1 pathway. (2). The expressions of B7-H1 in tumor tissues were enhanced by cisplatin. The expressions of B7-H1 were enhanced by PD-1 antibody. (3). The expressions of the quantity of Treg cells were suppressed in the spleen of mononuclear lymphocytes and CD8+T cells were raised in the tumor tissues by the treatment of PD-1 antibodies combined with cisplatin. (4) The anti-tumor effect and anti-tumor immunity of cisplatin were enhanced by blocking B7-H1/PD-1 pathway with PD-1 antibody.