Characterization of Surgery-Induced Vaccine Dysfunction in a Therapeutic Murine Melanoma Model

• Main Author: Lansdell, Casey
• Other Authors: Auer, Dr. Rebecca
• Language: en
• Published: Université d'Ottawa / University of Ottawa 2016
• Subjects: Cancer; Surgery; T cells; Immune system
• Online Access: http://hdl.handle.net/10393/34269; http://dx.doi.org/10.20381/ruor-5627

Surgical resection is the leading treatment of most solid tumours, however surgical stress creates an immunosuppressive environment that promotes metastases. A global decrease in T cell numbers and function post-surgery has been documented. However, the effect on tumour associated antigen (TAA)-specific T cells remains unclear. The objective is therefore to evaluate the impact of surgical stress on TAA-specific adaptive T cell immunity. Melanoma tumour-bearing C57BL/6 mice were vaccinated using AdhDCT, an adenovirus expressing dopochrome totaumerase (DCT), a melanoma TAA, and underwent abdominal nephrectomies to induce surgical stress. Surgical stress decreased the number of splenic cytotoxic T cells (CTLs) and their capacity to produce immunostimulatory cytokines (IFNγ and TNFα), as determined by flow cytometry. A perioperative accumulation in CTL-suppressive MDSCs was observed and demonstrated a direct suppression of CTL IFNγ and TNFα production and secretion. Understanding the mechanisms of perioperative T cell dysfunction will facilitate the development of targeted immunotherapies.