VSV∆M51 drives CD8+ T cell-mediated tumour regression through infection of both cancer and non-cancer cells
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)<sup>ΔM51</sup>-sensitive and VSV<sup>ΔM51</sup>-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<sup>+</sup> 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.
Authors
- Gerone A. Gonzales
- Madison Turk (ORCID: https://orcid.org/0000-0001-9195-8406)
- Douglas J. Mahoney (ORCID: https://orcid.org/0000-0002-0642-992X)
- Johnathan Canton (ORCID: https://orcid.org/0000-0001-8869-8404)
- Daniil A. Vishnevskiy (ORCID: https://orcid.org/0000-0002-5778-215X)
- Jahanara Rajwani (ORCID: https://orcid.org/0000-0003-3409-4319)
- Martin Hyrcza
- Keith C.K. Lau (ORCID: https://orcid.org/0000-0001-7870-6597)
- Craig N. Jenne (ORCID: https://orcid.org/0000-0001-8637-0181)
- Shannon Snelling (ORCID: https://orcid.org/0000-0002-2504-235X)
- Chris Gafuik
- Hayley M. Todesco (ORCID: https://orcid.org/0000-0002-6905-3667)
- Dae‐Sun Kim
- Pinaki Bose (ORCID: https://orcid.org/0000-0002-8338-2838)
- Laura Mah
- Jingna Xue (ORCID: https://orcid.org/0000-0002-5981-1938)
- Jennifer A. Chan (ORCID: https://orcid.org/0000-0001-9798-1551)
- Franz J. Zemp (ORCID: https://orcid.org/0000-0002-8845-3535)
- Michael J. Monument (ORCID: https://orcid.org/0000-0002-9517-8308)
- Victor Naumenko (ORCID: https://orcid.org/0000-0003-0192-4574)
- Ayan Chanda (ORCID: https://orcid.org/0000-0002-2692-8558)
- Kyle Potts (ORCID: https://orcid.org/0000-0002-4991-6402)
- Karys Hildebrand (ORCID: https://orcid.org/0000-0002-1075-7950)
- Shan Liao
Institutions
- University of Calgary (CA)
- Alberta Children's Hospital (CA)
- Alberta Bone and Joint Health Institute (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-15
- DOI
- https://doi.org/10.1038/s41467-024-54111-6
- Citations
- 11
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 2.65
Funders
- Children's Hospital Foundation
- American College Health Foundation
- Alberta Children's Hospital Foundation
- National Institutes of Health
- Canadian Institutes of Health Research
- Canadian Cancer Society Research Institute