Chronic antigen in solid tumors drives a distinct program of T cell residence

Noah V. Gavil, Milcah C. Scott, Eyob Weyu, Olivia C. Smith, Stephen D. O’Flanagan, Sathi Wijeyesinghe, Sahar Lotfi-Emran, Stephen L. Shiao, Vaiva Vezys, David Masopust

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Analyses of healthy tissue reveal signatures that identify resident memory CD8+ T cells (TRM), which survey tissues without recirculating. The density of TRM phenotype cells within solid tumors correlates favorably with prognosis, suggesting that intratumoral residents control cancer. However, residence has not been directly tested, and intratumoral TRM phenotype cells could instead reflect aspects of the microenvironment that correlate with prognosis. Using a breast cancer model in mice, we found that conventional TRM markers do not inform the tumor residence of either bystander or tumor-specific cells, which exhibit further distinct phenotypes in the tumor microenvironment and healthy mammary tissue. Rather, tumor-specific, stem progenitor CD8+ T cells migrate to tumors and become resident while acquiring select markers of exhaustion. These data indicate that tonic antigen stimulation and the tumor environment drive distinct programs of residence compared with healthy tissues and that tumor immunity is sustained by continued migration of tumor-specific stem cells.

Original languageEnglish (US)
Article numbereadd5976
JournalScience Immunology
Volume8
Issue number84
DOIs
StatePublished - Jun 2023

Bibliographical note

Funding Information:
We thank past and present members of the Masopust and Vezys laboratories for support, discussions, and insights. We thank T. Freedman (University of Minnesota) and Z. Hartman (Duke University) for providing EO771 and EO771.ova cell lines, respectively. We thank the Imaging Core, Flow Cytometry Resource core, Minnesota Supercomputing Institute (M. Macchietto and A. Herman), and the University of Minnesota Genomics Center (E. Stanley and J. Garbe) at the University of Minnesota. Special thanks to Z. Steier from A. Shalek’s laboratory at the Massachusetts Institute of Technology for informatics advising. Additional thanks to the University of Minnesota’s Center for Immunology, which supports a collegial and collaborative environment for faculty and trainees alike. This work was supported by National Institutes of Health grants R01CA238439 and R01AI146032 (to D.M.), National Institutes of Health grant F30FA253992 (to N.V.G.), National Institutes of Health grant F31AI152353 (to M.C.S.), and National Institutes of Health grant R01CA238439-03S1 (to E.W.).

Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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