tetano
Editor, Senior Moderator
Clin Cancer Res. 2013 Jul 23. [Epub ahead of print]
Perioperative influenza vaccination reduces post-operative metastatic disease by reversing surgery-induced dysfunction in natural killer cells.
Tai LH, Zhang J, Scott KJ, Tanese de Souza C, Alkayyal AA, Abhirami Ananth A, Sahi S, Adair RA, Bakur Mahmoud A, Sad S, Bell JC, Makrigiannis AP, Melcher AA, Auer R.
Source
Ottawa Hospital Research Institute, Center for Innovative Cancer Research.
Abstract
PURPOSE:
Surgical removal of solid primary tumors is an essential component of cancer treatment. Surgery-induced dysfunction in NK cells has been linked to the development of metastases in animal models and cancer patients. 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 demonstrated as proof-of-principle that perioperative administration of a non-specific 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.
CONCLUSIONS:
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.
PMID:
23881927
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23881927
Perioperative influenza vaccination reduces post-operative metastatic disease by reversing surgery-induced dysfunction in natural killer cells.
Tai LH, Zhang J, Scott KJ, Tanese de Souza C, Alkayyal AA, Abhirami Ananth A, Sahi S, Adair RA, Bakur Mahmoud A, Sad S, Bell JC, Makrigiannis AP, Melcher AA, Auer R.
Source
Ottawa Hospital Research Institute, Center for Innovative Cancer Research.
Abstract
PURPOSE:
Surgical removal of solid primary tumors is an essential component of cancer treatment. Surgery-induced dysfunction in NK cells has been linked to the development of metastases in animal models and cancer patients. 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 demonstrated as proof-of-principle that perioperative administration of a non-specific 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.
CONCLUSIONS:
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.
PMID:
23881927
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23881927