小柯机器人

美国斯克里普斯研究所Peng Wu、Jie P. Li等研究人员合作通过相互作用依赖性岩藻糖基生物素化实现肿瘤抗原特异性T细胞的检测。相关论文于2020年10月22日在线发表在《细胞》杂志上。

据研究人员介绍，肿瘤特异性抗原（TSA）反应性T细胞的重新激活和克隆扩增对于检查点阻断和基于肿瘤浸润性淋巴细胞（TIL）的疗法的过继转移的成功至关重要。由于其异质组成，没有可靠的标记物可以特异性鉴定TSA反应性T细胞的组成。

研究人员开发了FucoID作为检测内源性抗原特异性T细胞以研究其生物学的通用平台。通过这种相互作用依赖性标记方法，可以检测到瘤内TSA反应性CD4⁺、CD8⁺T细胞和TSA抑制性CD4⁺T细胞，并根据旁观者T细胞的细胞表面酶促岩藻糖基生物素化作用将其与旁观者分离。

与旁观者TIL相比，TSA反应性TIL具有独特的T细胞受体（TCR）库和独特的基因特征。TSA反应性CD8⁺TIL虽然表现出功能障碍的表型，但具有实质性的增殖和肿瘤特异性杀伤能力。FucoID具有无遗传操作程序和快速周转的特点，并具有加速个性化癌症治疗步伐的潜力。

附：英文原文

Title: Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation

Author: Zilei Liu, Jie P. Li, Mingkuan Chen, Mengyao Wu, Yujie Shi, Wei Li, John R. Teijaro, Peng Wu

Issue&Volume: 2020-10-22

Abstract: Re-activation and clonal expansion of tumor-specific antigen (TSA)-reactive T cellsare critical to the success of checkpoint blockade and adoptive transfer of tumor-infiltratinglymphocyte (TIL)-based therapies. There are no reliable markers to specifically identifythe repertoire of TSA-reactive T cells due to their heterogeneous composition. Weintroduce FucoID as a general platform to detect endogenous antigen-specific T cellsfor studying their biology. Through this interaction-dependent labeling approach,intratumoral TSA-reactive CD4+, CD8+ T cells, and TSA-suppressive CD4+ T cells can be detected and separated from bystander T cells based on their cell-surfaceenzymatic fucosyl-biotinylation. Compared to bystander TILs, TSA-reactive TILs possessa distinct T cell receptor (TCR) repertoire and unique gene features. Although exhibitinga dysfunctional phenotype, TSA-reactive CD8+ TILs possess substantial capabilities of proliferation and tumor-specific killing.Featuring genetic manipulation-free procedures and a quick turnover cycle, FucoIDshould have the potential of accelerating the pace of personalized cancer treatment.

DOI: 10.1016/j.cell.2020.09.048

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31245-9#%20