Effect Of Radiotherapy Combined With Anti-PD-L1 On The Expression Of IL-22 In Mouse Colon Tumor Microenvironment

ObjectiveRadiotherapy combined with anti-PD-L1 can not only enhance the anti-tumor immune response,but also improve the tumor immune microenvironment,resulting in abscopal effect to inhibit distant tumors.Interleukin-22(IL-22),a cytokine secreted mainly by helper T cell22(Th22),plays an important role in the occurrence and development of malignant tumors.In this study,the antitumor effect and abscopal effect of radiotherapy combined with anti-PD-L1were observed,and the expression of cytokine IL-22 and CD8~+T cells in mouse colon cancer tumor microenvironment was detected.To investigate the possible mechanism of antitumor effect and abscopal effect of radiotherapy combined with anti-PD-L1.Materials and methodsThe mouse colon cancer MC38 cell line was routinely cultured and injected subcutaneously into the left hind limb of C57BL/c mice as the first tumor.Three days later,the right hind limb of the mouse was subcutaneously injected with the same number of mouse colon tumor MC38 cells as the second tumor.To establish an animal model of subcutaneous transplantation of colon tumor in mice.Establish an animal model of subcutaneous transplantation of colon tumor in mice.After the 11th day,they were randomly divided into 4groups(A:radiotherapy group,B:radiotherapy combined with anti-PD-L1 group,C:anti-PD-L1 group,D:control group).On the 12th day,tumors of group A and group B locally received 8Gy dose every day for a total of three times.On the 18th day,group B and group C received 200?g anti–PD-L1 every three days for a total of four times.The tumor volume was measured every 3 days.On the 35th day,the mice were killed by cervical vertebra dislocation.The second tumor tissue of mice was taken for experiment.The expression of IL-22 and CD8+T cells in mouse colon cancer tumor microenvironment was detected by immunohistochemistry technique.ResultsThe first tumor of tumor-bearing mice in group B was significantly reduced or even disappeared,while the first tumor of group A and group C was not significantly reduced.The second tumor growth of tumor-bearing mice in group B was significantly slower than that in group A and group C.Immunohistochemical staining of the second tumor tissue showed that the expression of cytokine IL-22 in group B was significantly lower than that of other groups(Group A:16610.15±2671.897,Group B:13112.76±954.352,Group C:17363.30±1889.805,Group D:18595.93±3468.289).The CD8~+T cells in the second tumor tissue of tumor mice was significantly higher than that of other groups(Group A:27529.05±2395.501,Group B:37161.98±6665.989,Group C:27473.89±3665.566,Group D:24397.50±6163.696).ConclusionRadiotherapy combined with anti-PD-L1 can effectively inhibit tumor growth and induce abscopal effect at the same time.The possible mechanism is to enhance the anti-tumor effect of the body,by reducing the expression of IL-22 and increasing the content of CD8~+T cells in the tumor immune microenvironment.