决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Microbiota-targeted nanoplatforms for colorectal cancer immunotherapy.
结直肠癌(CRC)仍是全球主要的健康负担,免疫治疗疗效常受到免疫抑制性肿瘤微环境(TME)的限制。
结直肠癌(CRC)仍是全球主要的健康负担,免疫治疗疗效常受到免疫抑制性肿瘤微环境(TME)的限制。新出现的证据强调了肠道微生物群在塑造肿瘤进展和治疗反应中的关键作用。本综述首先总结了肠道微生物群与CRC免疫微环境之间的双向串扰,详细阐述了特定微生物物种和代谢物如何通过NF- B、RIG-I乳酸化、AhR和cGAS-STING等通路调控关键免疫细胞(MDSCs、Tregs、TAMs、DCs、CD8 T细胞和CD4 T细胞)。基于这些见解,我们随后探讨了微生物群靶向纳米平台(脂质/蛋白质基、聚合物基和无机系统),这些平台能够精确调控微生物组成和功能。这些纳米平台通过重塑微生物群和重编程TME,与免疫检查点抑制剂、癌症疫苗、CAR-T细胞和溶瘤病毒产生协同作用。尽管临床前结果令人鼓舞,但仍存在挑战,包括微生物组异质性、生物安全性问题、临床转化缓慢以及药代动力学障碍。总体而言,微生物群靶向纳米平台代表了一种改善CRC免疫治疗的新型整合策略。
Colorectal cancer (CRC) remains a major global health burden, and immunotherapy efficacy is often restricted by an immunosuppressive tumor microenvironment (TME). Emerging evidence highlights the pivotal role of the gut microbiota in shaping tumor progression and therapeutic responses. This review first summarizes the bidirectional crosstalk between gut microbiota and the CRC immune microenvironment, detailing how specific microbial species and metabolites regulate key immune cells (MDSCs, Tregs, TAMs, DCs, CD8 T cells, and CD4 T cells) through pathways such as NF- B, RIG-I lactylation, AhR, and cGAS-STING. Based on these insights, we then examine microbiota-targeted nanoplatforms (lipid/protein-based, polymer-based, and inorganic systems) that enable precise modulation of microbial composition and function. These nanoplatforms synergize with immune checkpoint inhibitors, cancer vaccines, CAR-T cells, and oncolytic viruses by reshaping the microbiota and reprogramming the TME. Despite promising preclinical outcomes, challenges remain, including microbiome heterogeneity, biosafety concerns, slow clinical translation, and pharmacokinetic hurdles. Overall, microbiota-targeted nanoplatforms represent a novel and integrative strategy to improve CRC immunotherapy.
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