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.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/34269 |
| Date | January 2016 |
| Creators | Lansdell, Casey |
| Contributors | Auer, Dr. Rebecca, Bell, Dr. John |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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