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:Harnessing exosomes: From tumor immune escape to therapeutic innovation in gastric cancer immunotherapy.
胃癌在全球最常见癌症中排名第五,预后不佳。
胃癌是全球第五大常见癌症,预后极差。近年来,免疫疗法,特别是免疫检查点抑制剂,为晚期胃癌患者带来一线希望。然而,并非所有患者都能从该类治疗中获益,因为肿瘤微环境会显著影响疗效。外泌体是细胞间通讯的重要介质,在塑造和调节肿瘤微环境方面具有复杂多样的作用。本综述全面概述外泌体在胃癌肿瘤微环境中的功能机制,深入探讨其生物发生、功能及其对先天性和适应性免疫细胞(如树突状细胞、髓源性抑制细胞和T细胞)及癌症相关成纤维细胞的影响。此外,本文还探讨外泌体在胃癌免疫治疗中的潜在应用,包括作为预测免疫检查点抑制剂疗效的生物标志物、药物递送载体,以及用于开发外泌体疫苗和基因疗法。值得注意的是,本综述强调外泌体具有双重作用:其可促进肿瘤免疫逃逸,但也是创新治疗策略的有前景靶点。本文还比较潜在的外泌体疗法与现有免疫疗法(如免疫检查点抑制剂)及新兴CAR-T细胞疗法。最后,作者展望外泌体在胃癌精准免疫治疗中的未来发展,为这一新兴领域提供前瞻性视角。
Gastric cancer ranks fifth among the most prevalent cancers globally, with a dismal prognosis. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has emerged as a glimmer of hope for advanced gastric cancer patients. However, not all patients can benefit from this treatment modality, as the tumor microenvironment significantly influences treatment efficacy. Exosomes, pivotal mediators of intercellular communication, exert intricate and diverse effects in shaping and regulating the tumor microenvironment. This review provides a comprehensive overview of the functional mechanisms of exosomes within the gastric cancer tumor microenvironment. It delves into their biogenesis, functions, and impact on innate and adaptive immune cells (such as dendritic cells, myeloid-derived suppressor cells, and T cells) and cancer-associated fibroblasts. Additionally, the potential applications of exosomes in gastric cancer immunotherapy are explored, including their use as biomarkers to predict responses to immune checkpoint inhibitors, and drug delivery vectors, and in the development of exosome-based vaccines and gene therapy. Notably, this review emphasizes the dual nature of exosomes: they can facilitate tumor immune escape, yet they also serve as promising targets for innovative therapeutic strategies. It also compares potential exosome-based strategies with existing immunotherapies like ICIs and emerging CAR-T cell therapies. Finally, insights into the future of exosomes in precision immunotherapy for gastric cancer are offered, presenting a forward-looking perspective on this emerging field.
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