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Tumor-reprogrammed resident T cells resist radiation to control tumors

Author

Listed:
  • Ainhoa Arina

    (The University of Chicago)

  • Michael Beckett

    (The University of Chicago)

  • Christian Fernandez

    (The University of Chicago)

  • Wenxin Zheng

    (The University of Chicago)

  • Sean Pitroda

    (The University of Chicago)

  • Steven J. Chmura

    (The University of Chicago)

  • Jason J. Luke

    (The University of Chicago)

  • Martin Forde

    (The University of Chicago)

  • Yuzhu Hou

    (The University of Chicago)

  • Byron Burnette

    (The University of Chicago)

  • Helena Mauceri

    (The University of Chicago)

  • Israel Lowy

    (Regeneron Pharmaceuticals)

  • Tasha Sims

    (Regeneron Pharmaceuticals)

  • Nikolai Khodarev

    (The University of Chicago)

  • Yang-Xin Fu

    (University of Texas Southwestern)

  • Ralph R. Weichselbaum

    (The University of Chicago)

Abstract

Successful combinations of radiotherapy and immunotherapy depend on the presence of live T cells within the tumor; however, radiotherapy is believed to damage T cells. Here, based on longitudinal in vivo imaging and functional analysis, we report that a large proportion of T cells survive clinically relevant doses of radiation and show increased motility, and higher production of interferon gamma, compared with T cells from unirradiated tumors. Irradiated intratumoral T cells can mediate tumor control without newly-infiltrating T cells. Transcriptomic analysis suggests T cell reprogramming in the tumor microenvironment and similarities with tissue-resident memory T cells, which are more radio-resistant than circulating/lymphoid tissue T cells. TGFβ is a key upstream regulator of T cell reprogramming and contributes to intratumoral Tcell radio-resistance. These findings have implications for the design of radio-immunotherapy trials in that local irradiation is not inherently immunosuppressive, and irradiation of multiple tumors might optimize systemic effects of radiotherapy.

Suggested Citation

  • Ainhoa Arina & Michael Beckett & Christian Fernandez & Wenxin Zheng & Sean Pitroda & Steven J. Chmura & Jason J. Luke & Martin Forde & Yuzhu Hou & Byron Burnette & Helena Mauceri & Israel Lowy & Tasha, 2019. "Tumor-reprogrammed resident T cells resist radiation to control tumors," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11906-2
    DOI: 10.1038/s41467-019-11906-2
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    Cited by:

    1. Nils-Petter Rudqvist & Maud Charpentier & Claire Lhuillier & Erik Wennerberg & Sheila Spada & Caroline Sheridan & Xi Kathy Zhou & Tuo Zhang & Silvia C. Formenti & Jennifer S. Sims & Alicia Alonso & Sa, 2023. "Immunotherapy targeting different immune compartments in combination with radiation therapy induces regression of resistant tumors," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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