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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Innate immunity in tumour immunoediting and immunosurveillance.
Innate immunity in tumour immunoediting and immunosurveillance.
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癌症免疫疗法的成功激发了旨在增加免疫应答性癌症数量的研究。首批有效的免疫治疗策略——免疫检查点阻断(ICB)和 CAR-T 细胞——旨在克服 CD8+ T 细胞识别和杀伤肿瘤细胞的局限性。然而,大多数实体瘤仍然对这些措施无应答,需要新的治疗方法。肿瘤演化出许多策略来逃避免疫控制。识别免疫治疗策略的一种方法是研究免疫治疗应答性与无应答性肿瘤之间的区别。另一种方法是识别在免疫健全与免疫缺陷宿主中暴露于致癌物后出现的肿瘤差异。还有一种方法是识别新发肿瘤中使其能够逃避免疫监视(称为肿瘤免疫编辑)的基因表达变化。演化中的肿瘤抑制抗原加工和呈递以逃避触发肿瘤特异性 T 细胞,但也抑制向免疫细胞传递危险信号的关键先天免疫基因。在本视角中,我们讨论先天免疫在抗肿瘤反应中的作用,并思考如何利用先天免疫使肿瘤更具免疫应答性。
The successes of cancer immunotherapy have inspired research aiming to increase the number of immune-responsive cancers. The first effective immunotherapeutic strategies-immune checkpoint blockade (ICB) and CAR T cells-were designed to overcome limitations in CD8 + T cell recognition and killing of tumor cells.
However, most solid tumors still do not respond to these measures and new treatment approaches are needed. Tumors evolve many strategies to avoid immune control. One way to identify immunotherapy strategies is to study what distinguishes immunotherapy-responsive and -unresponsive tumors. Another way is to identify the differences in tumors that emerge after carcinogen exposure in immunocompetent versus immunodeficient hosts.
Still another way is to identify changes in gene expression in emerging tumors that enable them to escape immunosurveillance (known as tumor immunoediting). Evolving tumors suppress antigen processing and presentation to avoid triggering tumor-specific T cells but also repress key innate immune genes that transmit danger signals to immune cells. In this perspective, we discuss the roles of innate immunity in anti-tumor responses and consider how innate immunity could be harnessed to make tumors more immune-responsive.
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