CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor microenvironment and immunotherapy: from bench to bedside.
Tumor microenvironment and immunotherapy: from bench to bedside.
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肿瘤微环境(TME)由多种细胞和细胞外成分构成,具有多面性且不断变化。这些组分与恶性肿瘤的发生、进展及治疗密切相关。TME的特征包括异常血管、改变的细胞外基质、免疫细胞、分泌因子,以及癌症相关成纤维细胞和巨噬细胞。肿瘤微环境对理解癌症病程和治疗耐药的重要性已得到强调。TME可通过诱导调节性T细胞、髓源性抑制细胞(MDSC)及PD-L1等检查点分子表达等免疫抑制机制,抑制免疫应答并促进肿瘤存活。近期研究聚焦于理解TME内免疫细胞之间的相互作用,以开发重塑这一环境并提高免疫治疗效能的策略。
然而,免疫抑制性TME常妨碍免疫治疗策略发挥作用。本文探讨这些动态变化如何推动开发重编程TME、增强抗肿瘤免疫应答的新型免疫治疗策略。靶向TME的治疗方法,如免疫检查点阻断(ICB)、代谢抑制剂及免疫代谢关键酶,已用于癌症免疫治疗。
此外,CAR-T 细胞疗法、溶瘤病毒及细胞因子介导的TME调节等新兴疗法也显示出良好前景。本综述概述TME及其组成、对免疫治疗结局的影响,以及通过重塑TME增强疗效的新兴方法。
The tumor microenvironment (TME) is a multifaceted and ever-changing assemblage of cells and extracellular constituents. These components are closely linked to the onset and progression of malignancies, as well as their treatment. The TME is characterized by aberrant vasculature, altered extracellular matrix, immune cells, secreted factors, and cancer-associated fibroblasts and macrophages. The importance of the tumor microenvironment (TME) in understanding the course of cancer and resistance to treatment has been highlighted.
The TME can suppress immune responses and promote tumor survival by inducing immunosuppressive mechanisms, such as regulatory T cells, myeloid-derived suppressor cells (MDSCs), and checkpoint molecule expression (e. g. , PD-L1). Recent research has focused on understanding the interactions between immune cells within the TME to develop strategies that can remodel this environment and increase the effectiveness of immunotherapy.
However, the efficacy of immunotherapeutic strategies is frequently hindered by the immunosuppressive nature of the TME. This abstract explores how these dynamics have led to the development of novel immunotherapeutic strategies aimed at reprogramming the TME to enhance antitumor immune responses. Novel approaches targeting TME therapy, such as immune checkpoint blockade (ICB), metabolic inhibitors, and key enzymes of immune metabolism, have been used to treat of cancer immunotherapy.
Additionally, new and promising treatments including CAR-T cell therapy, oncolytic viruses, and cytokine-mediated TME modulation have shown promising results. This review provides a general overview of the TME, its components, its impact on immunotherapy outcomes, and emerging approaches to enhance therapeutic efficacy by remodeling the TME.
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