Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Cell. 2020 Nov 12;183(4):1117-1133.e19. doi: 10.1016/j.cell.2020.09.048. Epub 2020 Oct 22.
Re-activation and clonal expansion of tumor-specific antigen (TSA)-reactive T cells are critical to the success of checkpoint blockade and adoptive transfer of tumor-infiltrating lymphocyte (TIL)-based therapies. There are no reliable markers to specifically identify the repertoire of TSA-reactive T cells due to their heterogeneous composition. We introduce FucoID as a general platform to detect endogenous antigen-specific T cells for 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-surface enzymatic fucosyl-biotinylation. Compared to bystander TILs, TSA-reactive TILs possess a distinct T cell receptor (TCR) repertoire and unique gene features. Although exhibiting a 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, FucoID should have the potential of accelerating the pace of personalized cancer treatment.
肿瘤特异性抗原（TSA）反应性 T 细胞的再激活和克隆扩增对于检查点阻断和过继转移肿瘤浸润淋巴细胞（TIL）为基础的治疗的成功至关重要。由于其异质性组成，没有可靠的标记物来专门识别 TSA 反应性 T 细胞的库。我们引入 FucoID 作为一种通用平台，用于检测内源性抗原特异性 T 细胞，以研究其生物学特性。通过这种依赖于相互作用的标记方法，可以根据其细胞表面酶法糖基化生物素化，从旁观者 T 细胞中检测和分离肿瘤内 TSA 反应性 CD4、CD8 T 细胞和 TSA 抑制性 CD4 T 细胞。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。尽管表现出功能失调的表型，但 TSA 反应性 CD8 TIL 具有实质性的增殖和肿瘤特异性杀伤能力。FucoID 具有无基因操作程序和快速周转周期的特点，有望加快个性化癌症治疗的步伐。
