肿瘤细胞来源的微颗粒介导卵巢癌的免疫治疗与化疗

Immunotherapy is the hope of tumor eradication. Chemotherapy-mediated tumor cell killing results in the release of tumor antigens and danger signals that provide potential new stategies for current tumor immunotherapy. However, such means is hindered by chemotherapy-induced immune damage. Our previous studies showed that tumor cell-derived microparticles acted as vectors and selectively delivered chemotherapeutic drugs to tumor cells, thus avoiding its side effect on normal cells. Based on this, using murine and human ovarian cancers as models and ovarian cancer cell-derived microparticles as object of study, this study is designed to elucidate the unique effects of microparticles in bridging tumor immunotherapy and chemotherapy. Three parts are included:(1)microparticles deliver drugs to selectively target tumor cells and result in the remodeling of tumor immune microenvironment; (2)as the derivative of tumor cells, how microparticles effect on the antitumor immune responses; and (3) how microparticles packaging drugs synergizes with other antitumor immunotherapeutic means to achieve a better treatment efficiency. From a new perspective of microparticles packaging drugs, this study might open new vistas in tumor immunotherapy and provide new ideas for chemo-immunotherapy against other tumor types.

肿瘤免疫治疗被认为是清除残余肿瘤的希望所在。化疗杀伤肿瘤细胞所释放的肿瘤抗原和危险信号有望为当前肿瘤免疫治疗注入新鲜血液，但这一策略受制于化疗诱发的免疫抑制。我们前期工作显示，肿瘤细胞来源的微颗粒（microparticles），能够作为载体将化疗药物靶向至肿瘤细胞，避免对正常细胞的破坏。在此基础上，本项目以小鼠和人卵巢癌为模型，以卵巢癌肿瘤细胞来源的微颗粒为主轴，深入研究微颗粒作为桥梁在肿瘤免疫治疗和化疗中的独特作用，包括：①微颗粒靶向化疗药物选择性杀伤肿瘤细胞，重塑肿瘤免疫微环境；②微颗粒作为肿瘤细胞的衍生物，自身在诱导抗肿瘤免疫中的作用；③微颗粒包裹化疗药物与其它抗肿瘤免疫治疗方案的协同作用。从微颗粒包裹化疗药物这一全新角度出发，本项目将拓展目前肿瘤免疫治疗的研究范围和研究策略，并为其它类型恶性肿瘤的免疫治疗联合化疗提供新的思路。

肿瘤免疫治疗被认为是清除残余肿瘤的希望所在。化疗杀伤肿瘤细胞所释放的肿瘤抗原和危险信号有望为当前肿瘤免疫治疗注入新鲜血液，但这一策略受制于化疗诱发的免疫抑制。肿瘤细胞来源的微颗粒（microparticles），能够作为载体将化疗药物靶向至肿瘤细胞，避免对正常细胞的破坏。在此基础上，本项目深入研究微颗粒作为桥梁在肿瘤免疫治疗和化疗中的独特作用，包括：(1) 微颗粒靶向化疗药物选择性杀伤肿瘤细胞，重塑肿瘤免疫微环境；(2) 微颗粒作为肿瘤细胞的衍生物，自身在诱导抗肿瘤免疫中的作用；(3) 微颗粒包裹化疗药物与其它抗肿瘤免疫治疗方案的协同作用; (4) 微颗粒作为肿瘤疫苗的抗肿瘤免疫效果及作用。从微颗粒包裹化疗药物及微颗粒作为肿瘤疫苗的全新角度出发，完成了多项研究成果，研究论文发表于《Nature Communications》、《Cell Research》、《Biomaterial》、《Cancer Research》、《Oncogene》、《OncoImmunology》等国际主流期刊。本项目拓展了目前肿瘤免疫治疗的研究范围和研究策略，并为其它类型恶性肿瘤的免疫治疗联合化疗提供新的思路。