Correlation Between Low-abscopal Effect And Immunosensitizationinduced By Radiotherapy

The abscopal effect refers to the clinical phenomenon that the tumor in the non-irradiated area shrinks or even disappears after radiotherapy.Current studies have found that although abscopal effect can be induced by radiation therapy in a variety of tumors,the clinical incidence is far below expectation.The abscopal effect is mainly caused by the specific killing effect on distant tumors via activated CD8~+T cell,which is induced by the in situ tumor vaccine that developed by radiation therapy.Due to the different basic immune status of different organisms or tumors,simple radiotherapy is not enough to cause sufficient immune response,and inhibition of the immune microenvironment that ultimately lead to the low incidence of abscopal effects.Low immune inducibility is the molecular basis for low abscopal effects.The purpose of this study is to find out the factors that produce and influence the abscopal effects,attempts to improve immune response through attempts to immunize adjuvants and to optimize its incidence.Exploring the immune mechanisms involved in low abscopal effects induced by radiotherapy and low immune sensitization in vivo.The experiment hypothesized that PD-1 monoclonal antibody combined with immunological adjuvant and GMCSF will increase the incidence of abscopal effects while the use of glucocorticoids may inhibit or counteract tumor immunity and abscopal effects.Methods:Firstly,a double tumor model of murine malignant melanoma was established to investigate the tumor volume change and overall survival of C57BL/6 mice.Flow cytometry was used to measure the contents of CD4~+Tcell,CD8~+Tcell and Treg in lymphocytes of spleen and tumor tissues.By calculating the ratio of CD4~+T cell to CD8~+T cell,Treg to CD4~+T cell,the immune response of each group was compared.The pathological sections of HE staining were used to compare the damage of lung tissue,tumor tissue and spleen before and after radiotherapy.Immunofluorescence was used to detect the expression of immune molecules in different organs and to observe lymphocyte infiltration.Results:Establishment and verification of the effectiveness of radiation therapy on the mouse animal model.The single application of PolyIC,was found to be irrelevant to the abscopal effect.However,the combined use of the three factors that PolyIC,GMCSF and PD-1 monoclonal antibodies dramatically increased the incidence of abscopal effects during radiotherapy.Dexamethasone antagonizes the abscopal effect induced by immune adjuvant.The occurrence of abscopal effects was negatively correlated with the ratio of CD4~+T cell to CD8~+T cell of infiltrating T cells in spleen and tumor cells,and negatively correlated with the ratio of Treg to CD4~+T cell.Conclusions:In this study,we have found that the established animal model repeated the abscopal effect in melanoma cells and the combination of immunoadjuvant increased the effect of abscopal effects,while dexamethasone partially inhibited the abscopal effect.The importance of this experiment is to provide a theoretical basis for future clinical trials of immunoadjuvants to improve the low state of abscopal effects,which provided data support for current clinical applications.