In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue

Zhi Li, Zewen K. Tuong, Isaac Dean, Claire Willis, Fabrina Gaspal, Rémi Fiancette, Suaad Idris, Bethany Kennedy, John R. Ferdinand, Ana Peñalver, Mia Cabantous, Syed Murtuza Baker, Jeremy W. Fry, Gianluca Carlesso, Scott A. Hammond, Simon J. Dovedi, Matthew R. Hepworth, Menna R. Clatworthy, David R. Withers

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Improving the efficacy of immune checkpoint therapies will require a better understanding of how immune cells are recruited and sustained in tumors. Here, we used the photoconversion of the tumor immune cell compartment to identify newly entering lymphocytes, determine how they change over time, and investigate their egress from the tumor. Combining single-cell transcriptomics and flow cytometry, we found that while a diverse mix of CD8 T cell subsets enter the tumor, all CD8 T cells retained within this environment for more than 72 h developed an exhausted phenotype, revealing the rapid establishment of this program. Rather than forming tumor-resident populations, non-effector subsets, which express TCF-1 and include memory and stem-like cells, were continuously recruited into the tumor, but this recruitment was balanced by concurrent egress to the tumor-draining lymph node. Thus, the TCF-1+ CD8 T cell niche in tumors is highly dynamic, with the circulation of cells between the tumor and peripheral lymphoid tissue to bridge systemic and intratumoral responses.
Original languageEnglish
Article numbere20210749
Number of pages27
JournalJournal of Experimental Medicine
Issue number6
Publication statusPublished - 26 Apr 2022

Bibliographical note

© 2022 Li et al.


  • CD8-Positive T-Lymphocytes
  • Humans
  • Immunotherapy
  • Lymphoid Tissue
  • Neoplasms
  • T-Lymphocyte Subsets


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