Exploratory Research And Analysis Of The Effects Of Cyclophosphamide Combined Radiotherapy And Immunotherapy On Abscopal Effect

The abscopal effect refers to the clinical phenomenon of tumor shrinkage or even disappearance of tumors in non-irradiated areas after radiotherapy of local tumors.A number of studies have revealed the phase of the large-fractionated(H-RT)phase.More traditional radiotherapy can cause immunogenic cell death(ICD)of tumor cells,and lead to the occurrence of anti-tumor immune response.At the same time,tumor immune microenvironment(Tumor Microenvironment,TME)and other theories have proposed that tumor immune effects are also related to a variety of membrane proteins and cellular inflammatory factors with immunoregulatory functions in the microenvironment,such as PDL-1 / PD-1,CTLA-4,IL-10,TNF,so TME is gradually regarded as an important direction to discover anti-tumor immune targets.Cyclophosphamide(CYC)has extensive clinical application as a traditional chemotherapeutic drug.In recent years,it has been found that Low Dose cyclophosephamide(LD-CYC)has specific killing effect on Tregs and has potential Combination therapy basis.Based on the results of the above research,this paper uses low-dose cyclophosphamide combined with PDL-1 monoclonal antibody(anti-PDL-1)and large-segment radiotherapy to explore whether LD-CYC promote abscopal effects.The incidence of effects and their underlying immunological mechanisms.The study hypothesized that low-dose cyclophosphamide combined with PDL-1 monoclonal antibody and a single large-segment radiotherapy could further increase the incidence of abscopal effects.Methods: First,a mouse(C57)dual tumor model was established using mouse-derived melanoma cells(B16),and the tumor growth curve and the survival time of the mice were recorded.At the same time,the peripheral blood of the mice was detected by flow cytometry The contents of CD4 + T cells,CD8 + T cells,and Tregs in tissues such as spleen,tumor,and other tissues,and the ratio of CD8 + T cells / CD4 + T cells and Treg cells / CD4 + T cells was calculated to compare the experimental and control groups.Antitumor immunity.At the same time,HE stained pathological sections and immunohistochemistry were used to help judge the research results.Results: A low dose of 100 mg of cyclophosphamide is a suitable dose for combination therapy.The combination therapy group can further prolong the survival of mice and inhibit tumor growth(P <0.05).In mouse tumor tissue and spleen tissue,compared with the LD-CYC + anti-PDL-1 + RT group and anti-PDL-1 + RT group,CD8 + T cells / CD4+ T cell results showed p <0.05,both There are statistical differences.Compared with LD-CYC + anti-PDL-1 + RT group and LD-CYC + anti-PDL-1 + RT +LD-CYC,the results of CD8 + T cells / CD4+ T cells showed p <0.05.The results suggest that LD-CYC can effectively improve anti-tumor immunity,and multiple applications of LD-CYC can further improve anti-tumor immunity.Conclusion: This study identified the appropriate dose of low-dose cyclophosphamide,and on this basis confirmed that low-dose cyclophosphamide can further inhibit tumor growth and increase the incidence of abscopal effects.More LD-CYC can not promote abscopal effect,but it can increase the tumor necrosis rate and prolong the survival time of mice.However,due to the limitations of the research,whether multiple large doses of radiation therapy can achieve better treatment results needs further verification.