人源化小鼠模型在肿瘤免疫治疗中的应用进展

癌症治疗难度大，死亡率高，是危害全球人类健康的主要疾病之一。近年来，肿瘤免疫治疗在临床上显示出良好前景，但肿瘤和机体免疫系统的相互作用机制，尤其是肿瘤微环境中的免疫因素还有待深入了解。动物模型可以有效模拟体内肿瘤免疫微环境，是肿瘤免疫新疗法研发的重要工具之一。然而，小鼠等实验动物的免疫系统与人类在构成和反应机制上存在明显差异，于是人源化动物模型应运而生。此文对人源化小鼠模型的应用进展以及未来肿瘤免疫治疗中小鼠模型的应用方向及有待解决的问题做一综述。     

Andrographolide potentiates PD-1 blockade immunotherapy by inhibiting COX2-mediated PGE2 release

Cancer immunotherapy has now become a first line therapy for several kinds of tumors. However, the clinical performance of immnuocheckpoint blockade therapy is usually limited by low response rate or side effects including cytokine storm. Andrographolide, a natural diterpenoid from Andrographis paniculata, has been used in Asia for treatment of bronchitis, paristhmitis and bacillary dysentery for its unique anti-inflammatory effect. However, its effect on anti-tumor immunity remains elusive. In this study, we found that andrographolide in combination with anti-PD-1 antibody showed a higher therapeutic benefit than individual therapy in murine xenograft model of CT26 colon cancer. Consequently, andrographolide and anti-PD-1 antibody co-treatment boosted the function of CD4⁺ and CD8⁺ T cells evidenced by considerable tissue infiltration, elevated IFN-γ secretion and enhanced expression of cytotoxic T-cell related molecules including FasL, perforin and Granzyme B, which significantly decreases the tumor load. Mechanistically, andrographolide treatment inhibited COX2 activity and PGE2 release both in vivo and in vitro, which augments anti-tumor efficiency of anti-PD-1 therapy. Finally, we confirmed that COX2 level in human colon cancer sample positively correlated with tumor-promoting factors. Our study here provides a potential combination strategy for immunotherapy against colorectal cancer.