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VSV∆M51 drives CD8+ T cell-mediated tumour regression through infection of both cancer and non-cancer cells

Author

Listed:
  • Jahanara Rajwani

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Daniil Vishnevskiy

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Madison Turk

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Victor Naumenko

    (Arnie Charbonneau Cancer Institute; University of Calgary)

  • Chris Gafuik

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Dae-Sun Kim

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary
    Cumming School of Medicine; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Laura K. Mah

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary
    Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Shannon Snelling

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary)

  • Gerone A. Gonzales

    (Cumming School of Medicine; University of Calgary
    Faculty of Veterinary Medicine; University of Calgary)

  • Jingna Xue

    (Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Ayan Chanda

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Kyle G. Potts

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary)

  • Hayley M. Todesco

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary)

  • Keith C. K. Lau

    (Cumming School of Medicine; University of Calgary)

  • Karys M. Hildebrand

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Cumming School of Medicine; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Jennifer A. Chan

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Department of Pathology and Laboratory Medicine; University of Calgary)

  • Shan Liao

    (Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Michael J. Monument

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Cumming School of Medicine; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Martin Hyrcza

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Department of Pathology and Laboratory Medicine; University of Calgary)

  • Pinaki Bose

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Cumming School of Medicine; University of Calgary
    Department of Oncology; University of Calgary)

  • Craig N. Jenne

    (Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Johnathan Canton

    (Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
    Cumming School of Medicine; University of Calgary
    Faculty of Veterinary Medicine; University of Calgary)

  • Franz J. Zemp

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary
    Cumming School of Medicine; University of Calgary)

  • Douglas J. Mahoney

    (Arnie Charbonneau Cancer Institute; University of Calgary
    Alberta Children’s Hospital Research Institute; University of Calgary
    Cumming School of Medicine; University of Calgary
    Cumming School of Medicine; University of Calgary)

Abstract

Oncolytic viruses (OV) are designed to selectively infect and kill cancer cells, while simultaneously eliciting antitumour immunity. The mechanism is expected to originate from infected cancer cells. However, recent reports of tumour regression unaccompanied by cancer cell infection suggest a more complex mechanism of action. Here, we engineered vesicular stomatitis virus (VSV)ΔM51-sensitive and VSVΔM51-resistant tumour lines to elucidate the role of OV-infected cancer and non-cancer cells. We found that, while cancer cell infections elicit oncolysis and antitumour immunity as expected, infection of non-cancer cells alone can also contribute to tumour regression. This effect is partly attributed to the systemic production of cytokines that promote dendritic cell (DC) activation, migration and antigen cross-presentation, leading to magnified antitumour CD8+ T cell activation and tumour regression. Such OV-induced antitumour immunity is complementary to PD-1 blockade. Overall, our results reveal mechanistic insights into OV-induced antitumour immunity that can be leveraged to improve OV-based therapeutics.

Suggested Citation

  • Jahanara Rajwani & Daniil Vishnevskiy & Madison Turk & Victor Naumenko & Chris Gafuik & Dae-Sun Kim & Laura K. Mah & Shannon Snelling & Gerone A. Gonzales & Jingna Xue & Ayan Chanda & Kyle G. Potts & , 2024. "VSV∆M51 drives CD8+ T cell-mediated tumour regression through infection of both cancer and non-cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54111-6
    DOI: 10.1038/s41467-024-54111-6
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    References listed on IDEAS

    as
    1. Judit Svensson-Arvelund & Sara Cuadrado-Castano & Gvantsa Pantsulaia & Kristy Kim & Mark Aleynick & Linda Hammerich & Ranjan Upadhyay & Michael Yellin & Henry Marsh & Daniel Oreper & Suchit Jhunjhunwa, 2022. "Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Matteo Iannacone & E. Ashley Moseman & Elena Tonti & Lidia Bosurgi & Tobias Junt & Sarah E. Henrickson & Sean P. Whelan & Luca G. Guidotti & Ulrich H. von Andrian, 2010. "Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus," Nature, Nature, vol. 465(7301), pages 1079-1083, June.
    3. Marie-Eve Wedge & Victoria A. Jennings & Mathieu J. F. Crupi & Joanna Poutou & Taylor Jamieson & Adrian Pelin & Giuseppe Pugliese & Christiano Tanese Souza & Julia Petryk & Brian J. Laight & Meaghan B, 2022. "Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Dae-Sun Kim & Himika Dastidar & Chunfen Zhang & Franz J. Zemp & Keith Lau & Matthias Ernst & Andrea Rakic & Saif Sikdar & Jahanara Rajwani & Victor Naumenko & Dale R. Balce & Ben W. Ewanchuk & Pankaj , 2017. "Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
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