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放疗作为提高实体瘤中 T 细胞疗法疗效的手段。

Radiotherapy as a means to increase the efficacy of T-cell therapy in solid tumors.

机构信息

Department of Radiation Oncology, Gustave Roussy Cancer Campus; UNICANCER, Villejuif, France.

INSERM U1030, Molecular Radiation Therapy and Therapeutic Innovation, Gustave Roussy Cancer Campus, University of Paris-Saclay, SIRIC SOCRATE, Villejuif, France.

出版信息

Oncoimmunology. 2022 Dec 22;12(1):2158013. doi: 10.1080/2162402X.2022.2158013. eCollection 2023.

Abstract

Chimeric antigen receptor (CAR)-T cells have demonstrated significant improvements in the treatment of refractory B-cell malignancies that previously showed limited survival. In contrast, early-phase clinical studies targeting solid tumors have been disappointing. This may be due to both a lack of specific and homogeneously expressed targets at the surface of tumor cells, as well as intrinsic properties of the solid tumor microenvironment that limit homing and activation of adoptive T cells. Faced with these antagonistic conditions, radiotherapy (RT) has the potential to change the overall tumor landscape, from depleting tumor cells to reshaping the tumor microenvironment. In this article, we describe the current landscape and discuss how RT may play a pivotal role for enhancing the efficacy of adoptive T-cell therapies in solid tumors. Indeed, by improving homing, expansion and activation of infused T cells while reducing tumor volume and heterogeneity, the use of RT could help the implementation of engineered T cells in the treatment of solid tumors.

摘要

嵌合抗原受体 (CAR)-T 细胞在治疗先前生存有限的难治性 B 细胞恶性肿瘤方面显示出显著改善。相比之下,针对实体瘤的早期临床研究令人失望。这可能是由于肿瘤细胞表面缺乏特异性和均匀表达的靶点,以及实体瘤微环境的固有特性限制了过继 T 细胞的归巢和激活。面对这些对抗性条件,放射治疗 (RT) 有可能改变整个肿瘤的状况,从消耗肿瘤细胞到重塑肿瘤微环境。在本文中,我们描述了当前的情况,并讨论了 RT 如何在增强过继性 T 细胞疗法在实体瘤中的疗效方面发挥关键作用。事实上,通过改善输注 T 细胞的归巢、扩增和激活,同时减少肿瘤体积和异质性,RT 的应用可以帮助在实体瘤的治疗中实施工程化 T 细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed07/9788698/c128e2120816/KONI_A_2158013_F0001_OC.jpg

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