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Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells

Author

Listed:
  • Brandon J. Burbach

    (University of Minnesota
    University of Minnesota
    University of Minnesota
    University of Minnesota)

  • Stephen D. O’Flanagan

    (University of Minnesota
    University of Minnesota
    University of Minnesota)

  • Qi Shao

    (University of Minnesota
    University of Minnesota
    University of Minnesota)

  • Katharine M. Young

    (University of Minnesota
    University of Minnesota)

  • Joseph R. Slaughter

    (University of Minnesota
    University of Minnesota)

  • Meagan R. Rollins

    (University of Minnesota
    University of Minnesota
    Boston Scientific Corporation)

  • Tami Jo L. Street

    (University of Minnesota
    University of Minnesota)

  • Victoria E. Granger

    (University of Minnesota
    University of Minnesota)

  • Lalit. K. Beura

    (University of Minnesota
    University of Minnesota
    Brown University)

  • Samira M. Azarin

    (University of Minnesota
    University of Minnesota
    University of Minnesota)

  • Satish Ramadhyani

    (BTG plc)

  • Bruce R. Forsyth

    (Boston Scientific Corporation)

  • John C. Bischof

    (University of Minnesota
    University of Minnesota
    University of Minnesota
    University of Minnesota)

  • Yoji Shimizu

    (University of Minnesota
    University of Minnesota
    University of Minnesota
    University of Minnesota)

Abstract

Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (TRM) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve neoantigen-specific CD8+ T cells and formation of a small population of non-recirculating TRM in several NLTs. Primary tumor destruction by irreversible electroporation (IRE), followed by anti-CTLA-4 immune checkpoint inhibitor (ICI), promotes robust expansion of tumor-specific CD8+ T cells in blood, tumor, and NLTs. Parabiosis studies confirm that TRM establishment following dual therapy is associated with tumor remission in a subset of cases and protection from subsequent tumor challenge. Addition of anti-PD-1 following dual IRE + anti-CTLA-4 treatment blocks tumor growth in non-responsive cases. This work indicates that focal tumor destruction using IRE combined with ICI is a potent in situ tumor vaccination strategy that generates protective tumor-specific TRM.

Suggested Citation

  • Brandon J. Burbach & Stephen D. O’Flanagan & Qi Shao & Katharine M. Young & Joseph R. Slaughter & Meagan R. Rollins & Tami Jo L. Street & Victoria E. Granger & Lalit. K. Beura & Samira M. Azarin & Sat, 2021. "Irreversible electroporation augments checkpoint immunotherapy in prostate cancer and promotes tumor antigen-specific tissue-resident memory CD8+ T cells," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24132-6
    DOI: 10.1038/s41467-021-24132-6
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    Cited by:

    1. Xiaoyu Liu & Yaping Zhuang & Wei Huang & Zhuozhuo Wu & Yingjie Chen & Qungang Shan & Yuefang Zhang & Zhiyuan Wu & Xiaoyi Ding & Zilong Qiu & Wenguo Cui & Zhongmin Wang, 2023. "Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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