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

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, Hayley M. Todesco, Keith C. K. Lau, Karys M. Hildebrand, Jennifer A. Chan, Shan Liao, Michael J. Monument, Martin Hyrcza, Pinaki Bose, Craig N. Jenne, Johnathan Canton, Franz J. Zemp and Douglas J. Mahoney ()
Additional contact information
Jahanara Rajwani: Arnie Charbonneau Cancer Institute; University of Calgary
Daniil Vishnevskiy: Arnie Charbonneau Cancer Institute; University of Calgary
Madison Turk: Arnie Charbonneau Cancer Institute; University of Calgary
Victor Naumenko: Arnie Charbonneau Cancer Institute; University of Calgary
Chris Gafuik: Arnie Charbonneau Cancer Institute; University of Calgary
Dae-Sun Kim: Arnie Charbonneau Cancer Institute; University of Calgary
Laura K. Mah: Arnie Charbonneau Cancer Institute; University of Calgary
Shannon Snelling: Arnie Charbonneau Cancer Institute; University of Calgary
Gerone A. Gonzales: Cumming School of Medicine; University of Calgary
Jingna Xue: Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
Ayan Chanda: Arnie Charbonneau Cancer Institute; University of Calgary
Kyle G. Potts: Arnie Charbonneau Cancer Institute; University of Calgary
Hayley M. Todesco: Arnie Charbonneau Cancer 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
Jennifer A. Chan: Arnie Charbonneau Cancer Institute; University of Calgary
Shan Liao: Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
Michael J. Monument: Arnie Charbonneau Cancer Institute; University of Calgary
Martin Hyrcza: Arnie Charbonneau Cancer Institute; University of Calgary
Pinaki Bose: Arnie Charbonneau Cancer Institute; University of Calgary
Craig N. Jenne: Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
Johnathan Canton: Joan and Phoebe Snyder Institute for Chronic Disease; University of Calgary
Franz J. Zemp: Arnie Charbonneau Cancer Institute; University of Calgary
Douglas J. Mahoney: Arnie Charbonneau Cancer Institute; University of Calgary

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54111-6

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