目前，脑胶质瘤具有高发病率和高致死率，严重威胁着人类健康。重离子放疗是一种被证明可有效控制脑胶质瘤的局部治疗方式，免疫治疗是具有广泛运用前景的新兴系统治疗方式，两者的联合对治疗脑胶质瘤具有重要的实用价值。放疗加剧的肿瘤炎症有利于招募中性粒细胞，且细菌外膜可搭乘中性粒细胞和用于抗肿瘤免疫治疗。因此，本项目在申请人前期研究基础上，设想吲哚胺-2,3-双加氧酶（IDO）抑制剂装载的细菌外膜可搭乘中性粒细胞靶向递送至重离子放疗后的脑胶质瘤，进而协同强化机体抗肿瘤免疫。在本项目中，拟实施基于载药细菌外膜的脑胶质瘤“重离子-免疫”联合治疗的探索，重点探讨重离子放疗对该纳米囊泡通过血脑屏障和对肿瘤靶向递送的影响及机制，系统阐述重离子放疗、细菌外膜和IDO抑制剂三者协同强化抗肿瘤免疫的作用机制。本项目探索了重离子放疗促进免疫治疗的一条新途径及其机制，将为脑胶质瘤的临床治疗提供具有潜在应用价值的策略和方法。

Currently, glioma with high morbidity and mortality is a serious threat to human health. Heavy ion radiotherapy is a local treatment that has been proved to be effective in controlling glioma. Immunotherapy is a new systematic therapy with wide application prospect. Thus, the combination therapy based on heavy ion radiotherapy and immunotherapy will be benefit to conquer glioma. The inflammation induced by radiotherapy is beneficial to the chemotaxis of neutrophils. Moreover, bacterial outer membrane nanoparticle which targets to in vivo neutrophils could be used for triggering anti-tumor immunotherapy. Herein, this project hypothesize that heavy ion radiotherapy can induce the glioma-targeted delivery of bacterial outer membrane nanoparticles carried indoleamine 2,3-dioxygenase (IDO) inhibitors for enhanced anti-tumor immunotherapy. In this project, we will conduct＂heavy ion – immune＂ combination therapy of glioma by using neutrophil-hitchhiked bacterial outer membrane nanoparticle carried IDO inhibitors. Additionally, the effect of heavy ion radiotherapy on glioma-targeted delivery of abovementioned nanoparticle and its inner mechanism will be mainly discussed. Meanwhile, the comprehensive mechanism of synergistic antitumor immunotherapy based on bacterial outer membrane, IDO inhibitors and heavy-ion radiotherapy will be investigated. Therefore, our project will explore a new approach of promoting immunotherapy under heavy ion exposure and its mechanism, providing potential practical strategies and methods for the clinical treatment of glioma.