IL6 Induces an IL22+ CD8+ T-cell Subset with Potent Antitumor Function

DOI PDF 1 Citations
  • Michael St. Paul
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Samuel D. Saibil
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Scott C. Lien
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • SeongJun Han
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Azin Sayad
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • David T. Mulder
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Carlos R. Garcia-Batres
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Alisha R. Elford
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Kavita Israni-Winger
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Céline Robert-Tissot
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Michael Zon
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Sarah Rachel Katz
    3Division of Gynecologic Oncology, University Health Network, Toronto, Ontario, Canada.
  • Patricia A. Shaw
    4Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Blaise A. Clarke
    4Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Marcus Q. Bernardini
    3Division of Gynecologic Oncology, University Health Network, Toronto, Ontario, Canada.
  • Linh T. Nguyen
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Benjamin Haibe-Kains
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Trevor J. Pugh
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
  • Pamela S. Ohashi
    1Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.

Description

<jats:title>Abstract</jats:title><jats:p>CD8+ T cells can be polarized into several different subsets as defined by the cytokines they produce and the transcription factors that govern their differentiation. Here, we identified the polarizing conditions to induce an IL22-producing CD8+ Tc22 subset, which is dependent on IL6 and the aryl hydrocarbon receptor transcription factor. Further characterization showed that this subset was highly cytolytic and expressed a distinct cytokine profile and transcriptome relative to other subsets. In addition, polarized Tc22 were able to control tumor growth as well as, if not better than, the traditional IFNγ-producing Tc1 subset. Tc22s were also found to infiltrate the tumors of human patients with ovarian cancer, comprising up to approximately 30% of expanded CD8+ tumor-infiltrating lymphocytes (TIL). Importantly, IL22 production in these CD8+ TILs correlated with improved recurrence-free survival. Given the antitumor properties of Tc22 cells, it may be prudent to polarize T cells to the Tc22 lineage when using chimeric antigen receptor (CAR)-T or T-cell receptor (TCR) transduction–based immunotherapies.</jats:p>

Journal

  • Cancer Immunology Research

    Cancer Immunology Research 8 (3), 321-333, 2020-03-01

    American Association for Cancer Research (AACR)

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