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Perioperative Influenza Vaccination Reduces Postoperative Metastatic Disease by Reversing Surgery-Induced Dysfunction in Natural Killer Cells
Published version of a preprint
Abstract
Purpose: Surgical removal of solid primary tumors is an essential component of cancer treatment. Surgery-induced dysfunction in natural killer (NK) cells has been linked to the development of metastases in animal models and patients with cancer. We investigated the activation of NK cells using influenza vaccine in the perioperative period to eradicate micrometastatic disease. Experimental Design: Both the B16lacZ and 4T1 tumor models in immunocompetent mice were used to assess the in vivo efficacy of perioperative influenza vaccine administration. In healthy human donors and cancer surgery patients, we assessed NK cell function pre- and post-influenza vaccination using both in vivo and ex vivo assays. Results: Using the TLR3 agonist poly(I:C), we showed as proof-of-principle that perioperative administration of a nonspecific innate immune stimulant can inhibit surgery-induced dysfunction in NK cells and attenuate metastases. Next, we assessed a panel of prophylactic vaccines for NK cell activation and determined that inactivated influenza vaccine was the best candidate for perioperative administration. Perioperative influenza vaccine significantly reduced tumor metastases and improved NK cytotoxicity in preclinical tumor models. Significantly, IFNα is the main cytokine mediator for the therapeutic effect of influenza vaccination. In human studies, influenza vaccine significantly enhanced NK cell activity in healthy human donors and cancer surgery patients. Conclusion: These results provide the preclinical rationale to pursue future clinical trials of perioperative NK cell activation, using vaccination in cancer surgery patients. Research into perioperative immune therapy is warranted to prevent immune dysfunction following surgery and eradicate metastatic disease. Clin Cancer Res; 19(18); 5104–15. ©2013 AACR.
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“Intriguingly, Tai et al. found that administering a single dose of the influenza vaccine intramuscularly a day before surgery optimally activated NK cells in specific murine models.265”
From Drug repurposing for cancer therapy (2024) · cites this paper as [265]
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Metadata
- Authors
- Tai, L.-H., Zhang, J., Scott, K. J., de Souza, C. T., Alkayyal, A. A., Ananth, A. A., Sahi, S., Adair, R. A., Mahmoud, A. B., Sad, S., Bell, J. C., Makrigiannis, A. P., Melcher, A. A., & Auer, R. C.
- Affiliations
- University of Ottawa (CA)
- Corresponding author
- Auer, Rebecca C.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2013-09-15
- Volume
- 19
- Issue
- 18
- Pages
- 5104-5115
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2153129739
- Cited by
- 70
- References
- 39
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 2
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- natural killer cells, NK cell dysfunction, cancer surgery, metastasis, micrometastatic disease, NK cell activation, interferon-alpha, poly(I:C), TLR3 agonist, prophylactic vaccines, B16F10 melanoma, 4T1 breast cancer, cancer immunotherapy
- MeSH terms
- Animals, Cytotoxicity, Immunologic, Humans, Influenza Vaccines, Killer Cells, Natural, Lung Neoplasms, Lymphocyte Activation, Melanoma, Experimental, Mice, Inbred BALB C, Mice, Inbred C57BL, Postoperative Period, Surgical Procedures, Operative, Tumor Cells, Cultured, Vaccination, Mice, Knockout, Perioperative Care, Mice, Receptor, Interferon alpha-beta
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