Using cell-attached fucosyltransferase and a biotinylated (Bio+) substrate, Liu, Li, and Chen et al. developed FucoID, a proximity-labeling approach to specifically identify T cells binding to cognate antigen-presenting cells, allowing efficient capture of tumor antigen-specific TILs from multiple murine tumor models. The Bio+-enriched CD8+ T cells were PD-1+, possessed an exhaustion phenotype and a minor population of TCF1+ progenitor exhausted cells, and were more effective in tumor control than ‘bystander’ PD-1+ non-captured cells. Bio+-labeled CD4+ T cells contained target-reactive cells and a CD8+ T cell-suppressing (CD25+; presumably Treg) subpopulation.
Contributed by Ed Fritsch
ABSTRACT: 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.
Author Info: (1) Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. (2) Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92
Author Info: (1) Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. (2) 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. Electronic address: jieli@nju.edu.cn. (3) Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China. (4) Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China. (5) Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. (6) Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: pengwu@scripps.edu.
