The Mechanism Of P204 In Anti-tumor Immunity In Mice

p204,a member of p200 family which is induced by interferons(IFNs)in mice,gets involved in many important functions,such as promoting cell differentiation,inhibiting cell proliferation and sensing the invasion of double-strand DNA.And its human orthologue IFI16 has already been identified as an inhibitor of proliferation in many carcinoma cell lines.Herein,we used the first p204 knockout mice(short as KO)and wild type mice(short as WT)of same background building tumor-bearing mice with Lewis lung carcinoma(LLC)cells injected subcutaneously.We found impaired anti-tumor immunity in p204 knockout mice and summarized a primary network of p204 in regulating immune responses of tumor.Compared to WT tumor-bearing mice,the KO tumor-bearing group showed higher mortality,earlier decrease time of weight and larger weight loss after tumor removal,revealing that loss of p204 promoted the aggravation of tumor.And lung tissue histology analysis of tumor-bearing mice showed more severe inflammation in 12-week-old KO group and tumor metastasis in 32-week-old KO group,which confirms the aggravation of tumors in mice without p204 and indicates the importance of p204 in immune responses for tumor suppression.After tumor challenge,the subset ratio of helper T cells(Th)in spleen of KO mice was significantly reduced(p<0.001)while Th ratio of WT was stable.The rising amplitude of cytotoxic T cells in spleen of KO mice after LLC cells injection was also much lower than WT(p<0.001).Moreover,KO tumor-bearing mice had a larger decreased range of Th/Tc in spleen than WT.Based on these findings,we think that p204 probably participate in regulating T cells activity in tumor resisting.Through transcriptome analysis of spleen we found 492 differently expressed genes between WT and KO tumor-bearing mice.Further annotations and classifications revealed that p204 was closely related to inflammation,oxidative activity and transcriptional regulation.Knockout of p204 affected expressions of many genes related to Th cell immune activity in anti-tumor immunity.And p204 is also very likely to get involved in inhibiting oxidative responses to reduce the tumorigenesis risk.Constructed tumor-bearing model of p204 knockout mice with subcutaneously implanted tumor and transcriptome analysis of spleen in tumor-bearing mice without p204 were two main innovations of this study,which offered valuable information to understand the functions of p204 in regulation of anti-tumor immunity in details.In this thesis,we found that the connections between p204 and anti-tumor immunity mainly depend on the regulation of inflammation and T cell activity during the course of tumor.Thus we summarized the mechanism network of p204 in regulating anti-tumor immunity,which laid a solid foundation for further research on the role of p204 in immune response.