Surgical Stress Attenuates Pre-existing Anti-tumour Immunity Resulting in Postoperative Metastases and local Recurrence in a Murine Model

Abstract

Solid malignancies in cancer patients require surgical intervention; however, surgery has been shown to promote the metastatic potential of tumour cells. Surgery-induced impairment of adaptive immunity is poorly understood, thus, our aim is to characterize the impact of surgery on tumour antigen-specific cytotoxic T lymphocyte function. To generate anti-tumour immunity, we adopted a C57/B6 model of B16 melanoma immunized with intramuscular (IM) AdhDCT, an adenovirus expressing the melanoma-associated antigen human dopachrome tautomerase (hDCT). Surgical stress was induced by left abdominal nephrectomy. We found that surgery reduces overall survival in AdhDCT-immunized mice, whereas those that did not undergo surgery were cured of their tumours. Surgical stress also decreases both the proportion and absolute spleen numbers of DCT-specific IFN-gamma+ CD8+ T-cells by over 2-fold. We have shown that perioperative suppression of antigen-specific T-cells can lead to increased tumour burden in a murine melanoma model.