Study On The Role And Mechanism Of Compound P In Regulating Immunosuppressive Breast Tumors

Background: According to the latest global cancer statistics released by WHO International Cancer Research Institute in 2020,breast cancer has replaced lung cancer as the largest cancer incidence rate in the world.Whereas,in the statistics about women,the incidence rate and mortality rate of breast cancer is still the highest in the world.In recent years,tumor immunotherapy has gradually become another major therapy besides surgery,chemotherapy and radiotherapy.Immunotherapy has been studied for decades.The main limitation of immunotherapy is that most solid tumors have no response or limited response to it,such as breast cancer.Therefore,there is still a large gap in the research of tumor immunotherapy in the treatment of breast cancer.Due to the heterogeneity of breast cancer,the activation of innate or adaptive immune pathway is inhibited,so the treatment of breast cancer can start from enhancing the overall immunity.Methods: Firstly,we construct Balb/c mice model of homologous breast cancer 4T1 cell transplantation tumor,Balb/c mice model of compound Ppretreated 4T1 cell transplantation tumor and NSG mice model of homologous breast cancer 4T1 cell transplantation tumor to observe the occurrence and development of breast cancer.Then,we used transcriptome sequencing to obtain the differentially expressed genes of breast cancer between compound Ptreated group and normal saline control group,and then carried out bioinformatics analysis to determine the next step of mechanism research.Finally,flow cytometry,immunohistochemistry,fluorescence quantitative PCR and cell proliferation experiments were used to detect the content of A cells and C cells,and the expression levels of N and M molecules in the tumor of compound Pgroup and normal saline control group.At the cellular level,we also used fluorescence quantitative PCR to detect the mRNA expression level of N and M genes in several breast cancer cell lines.Results: The Balb/c mouse model of homologous breast cancer 4T1 xenografts and the Balb/c mouse model of compound Ppretreated 4T1 xenografts proved that compound Pat low dose(0.1 m L/0.3 m M)showed a surprising ability in inhibiting the occurrence and development of breast cancer.And then,the GSEA analysis of the differential genes obtained from the transcriptome sequencing results was significantly enriched the biological processes related to T cell activation.What's more,the results of flow cytometry showed that the content of A cells in compound Pgroup was significantly increased.The results of immunohistochemistry and RT-PCR showed that compound Psignificantly increased the expression level of M molecules.The proliferation of breast cancer cell line and NSG mouse model of 4T1 homologous xenograft tumor showed that compound Pdid not produce side effects.In conclusion,compound Pcan enhance the antigen presentation process by promoting the expression of M molecules and activating more A cells,so as to appropriately improve the overall immunity of mice and play an anti-tumor role.Conclusion: our experimental results preliminarily demonstrated that compound Phas anti-tumor effect and its mechanism,further proved the role of immune system in the prevention and treatment of breast cancer,and proposed a promising tumor immunotherapy that compound Pcan achieve tumor treatment by enhancing the overall immunity.