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:The Interplay between T Cells and Cancer: The Basis of Immunotherapy.
The Interplay between T Cells and Cancer: The Basis of Immunotherapy.
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在过去十年中,免疫疗法已成为癌症治疗中最具前景的方法之一。免疫检查点抑制剂的使用在多种癌症治疗中产生了令人印象深刻且持久的临床反应。
此外,利用嵌合抗原受体(CAR)工程化T细胞的免疫疗法在血液癌症中产生了强劲的反应,而T细胞受体(TCR)工程化T细胞在实体癌治疗中正显示出有前景的结果。尽管癌症免疫疗法取得了这些显著进展,但仍存在诸多挑战。部分患者群体对免疫检查点抑制剂治疗无反应,而CAR-T 细胞疗法尚未显示出对实体癌的疗效。在本综述中,我们首先讨论T细胞在机体防御癌症中所发挥的重要作用。随后,我们深入探讨当前免疫疗法面临挑战背后的机制,从免疫检查点上调导致的T细胞耗竭以及功能失调T细胞的转录和表观遗传景观变化开始。接着,我们讨论癌细胞内在特征,包括癌细胞的分子改变和肿瘤微环境(TME)的免疫抑制性质,这些共同促进了肿瘤细胞的增殖、存活、转移和免疫逃逸。
最后,我们审视癌症免疫疗法的最新进展,特别强调基于T细胞的治疗。
Over the past decade, immunotherapy has emerged as one of the most promising approaches to cancer treatment. The use of immune checkpoint inhibitors has resulted in impressive and durable clinical responses in the treatment of various cancers.
Additionally, immunotherapy utilizing chimeric antigen receptor (CAR)-engineered T cells has produced robust responses in blood cancers, and T cell receptor (TCR)-engineered T cells are showing promising results in the treatment of solid cancers. Despite these noteworthy advancements in cancer immunotherapy, numerous challenges remain.
Some patient populations are unresponsive to immune checkpoint inhibitor therapy, and CAR T cell therapy has yet to show efficacy against solid cancers. In this review, we first discuss the significant role that T cells play in the body's defense against cancer.
We then delve into the mechanisms behind the current challenges facing immunotherapy, starting with T cell exhaustion due to immune checkpoint upregulation and changes in the transcriptional and epigenetic landscapes of dysfunctional T cells.
We then discuss cancer-cell-intrinsic characteristics, including molecular alterations in cancer cells and the immunosuppressive nature of the tumor microenvironment (TME), which collectively facilitate tumor cell proliferation, survival, metastasis, and immune evasion.
Finally, we examine recent advancements in cancer immunotherapy, with a specific emphasis on T-cell-based treatments.
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