首页 > 分享 > 微生物组诱导逆转冷肿瘤以增强三阴性乳腺癌的免疫化学动力学治疗—小柯机器人—科学网

微生物组诱导逆转冷肿瘤以增强三阴性乳腺癌的免疫化学动力学治疗—小柯机器人—科学网

花匠小妙招
2024-11-26 17:14

微生物组诱导逆转冷肿瘤以增强三阴性乳腺癌的免疫化学动力学治疗

作者：小柯机器人发布时间：2023/11/23 10:29:11

中国科学院长春应化所曲晓刚团队报道了将肿瘤内细菌转化为免疫增强剂逆转冷肿瘤以增强三阴性乳腺癌的免疫化学动力学治疗。相关研究成果于2023年11月21日发表在《美国化学会志》。

三阴性乳腺癌（TNBC）的免疫治疗由于免疫“寒冷”的微环境导致治疗结果不令人满意。具核梭杆菌（F.nucleanum）被发现定植于三阴性乳腺肿瘤中，并能够免疫抑制肿瘤微环境和肿瘤转移。

该文中，研究人员构建了一种细菌衍生的外膜囊泡（OMV）涂层纳米平台，该平台精确靶向肿瘤组织，用于双重杀死有核F.nucleanum和癌症细胞，从而将瘤内细菌转化为TNBC免疫疗法中的免疫增强剂。所制备的纳米颗粒通过芬顿样反应有效诱导免疫原性细胞死亡，从而增强免疫原性。同时，甲硝唑可杀死瘤内F.nucleanum，导致病原体相关分子模式（PAMP）的释放。PAMP与OMV协同作用进一步促进了树突状细胞的成熟和随后的T细胞浸润。因此，“一举两得”策略温暖了寒冷的肿瘤环境，最大限度地提高了抗肿瘤免疫反应，实现了TNBC的有效治疗和转移预防。总的来说，这种基于肿瘤和正常组织微生态学差异以及微生物组诱导的冷肿瘤逆转的策略为TNBC的精确有效免疫治疗提供了新的见解。

附：英文原文

Title: Transforming Intratumor Bacteria into Immunopotentiators to Reverse Cold Tumors for Enhanced Immuno-chemodynamic Therapy of Triple-Negative Breast Cancer

Author: Xuemeng Liu, Mengyu Sun, Fang Pu, Jinsong Ren, Xiaogang Qu

Issue&Volume: November 21, 2023

Abstract: Immunotherapy of triple-negative breast cancer (TNBC) has an unsatisfactory therapeutic outcome due to an immunologically “cold” microenvironment. Fusobacterium nucleatum (F. nucleatum) was found to be colonized in triple-negative breast tumors and was responsible for the immunosuppressive tumor microenvironment and tumor metastasis. Herein, we constructed a bacteria-derived outer membrane vesicle (OMV)-coated nanoplatform that precisely targeted tumor tissues for dual killing of F. nucleatum and cancer cells, thus transforming intratumor bacteria into immunopotentiators in immunotherapy of TNBC. The as-prepared nanoparticles efficiently induced immunogenic cell death through a Fenton-like reaction, resulting in enhanced immunogenicity. Meanwhile, intratumoral F. nucleatum was killed by metronidazole, resulting in the release of pathogen-associated molecular patterns (PAMPs). PAMPs cooperated with OMVs further facilitated the maturation of dendritic cells and subsequent T-cell infiltration. As a result, the “kill two birds with one stone” strategy warmed up the cold tumor environment, maximized the antitumor immune response, and achieved efficient therapy of TNBC as well as metastasis prevention. Overall, this strategy based on a microecology distinction in tumor and normal tissue as well as microbiome-induced reversal of cold tumors provides new insight into the precise and efficient immune therapy of TNBC.

DOI: 10.1021/jacs.3c09472

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.3c09472