title: A mouse tumor model of surgical stress to explore the mechanisms of postoperative immunosuppression and evaluate novel perioperative immunotherapies.
abstract: Surgical resection is an essential treatment for most cancer patients, but surgery induces dysfunction in the immune system and this has been linked to the development of metastatic disease in animal models and in cancer patients. Preclinical work from our group and others has demonstrated a profound suppression of innate immune function, specifically NK cells in the postoperative period and this plays a major role in the enhanced development of metastases following surgery. Relatively few animal studies and clinical trials have focused on characterizing and reversing the detrimental effects of cancer surgery. Using a rigorous animal model of spontaneously metastasizing tumors and surgical stress, the enhancement of cancer surgery on the development of lung metastases was demonstrated. In this model, 4T1 breast cancer cells are implanted in the mouse mammary fat pad. At day 14 post tumor implantation, a complete resection of the primary mammary tumor is performed in all animals. A subset of animals receives additional surgical stress in the form of an abdominal nephrectomy. At day 28, lung tumor nodules are quantified. When immunotherapy was given immediately preoperatively, a profound activation of immune cells which prevented the development of metastases following surgery was detected. While the 4T1 breast tumor surgery model allows for the simulation of the effects of abdominal surgical stress on tumor metastases, its applicability to other tumor types needs to be tested. The current challenge is to identify safe and promising immunotherapies in preclinical mouse models and to translate them into viable perioperative therapies to be given to cancer surgery patients to prevent the recurrence of metastatic disease.
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
authors.forename: Lee-Hwa
authors.initials: LH
authors.lastname: Tai
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
authors.forename: Christiano
authors.initials: C
authors.lastname: Tanese de Souza
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute.
authors.forename: Shalini
authors.initials: S
authors.lastname: Sahi
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute; Department of Cellular and Molecular Medicine, University of Ottawa; Department of Neurosurgery, The Second Hospital of Shandong University.
authors.forename: Jiqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute; Department of Biochemistry, Microbiology and Immunology, University of Ottawa; Department of Medical Laboratory Technology, University of Tabuk.
authors.forename: Almohanad A
authors.initials: AA
authors.lastname: Alkayyal
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute; Department of Biochemistry, Microbiology and Immunology, University of Ottawa.
authors.forename: Abhirami Anu
authors.initials: AA
authors.lastname: Ananth
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute; Department of Surgery, Ottawa General Hospital; rauer@ottawahospital.on.ca.
authors.forename: Rebecca A C
authors.initials: RA
authors.lastname: Auer
mesh_terms: D000818:Animals; D005260:Female; D007114:Immunization / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D007252:Influenza Vaccines / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D051379:Mice; D009362:Neoplasm Metastasis; D009366:Neoplasm Seeding; D019990:Perioperative Care / Q000379:methods; D011183:Postoperative Complications / Q000276:immunology
chemical_list: D007252:Influenza Vaccines