Visceral Surgery Profoundly Affects the Cellular and Humoral Components of the Anti-Tumour Immune Response in a Murine Pancreatic Adenocarcinoma Model.

Abstract

Simple SummarySurgery is a fundamental part of the multimodal therapy concepts in oncological patients, especially in the early stage of pancreas tumour. There are numerous studies on the impact of primary tumour resection on the immune status, but to our knowledge, the impact of tumour-unrelated surgery on the anti-tumour immune response to the primary tumour it is not yet understood. Therefore, we used a murine model combining an orthotopically implanted adenocarcinoma of the pancreas and the model of surgically-induced immune dysfunction to assess the impact of postoperative immunosuppression on the growth of the primary tumour, on mortality and on the most important immune cell compartments in tumour defence. This knowledge might contribute to a basic understanding of the interaction of the primary tumour and the immune system and could guide new approaches to therapeutic strategies.(1) Background: Surgery is the most important element of multimodal treatment concepts in oncological patients, especially in the early stages of pancreatic tumours. While the influence of primary tumour resection on the immune status was analysed in several studies, the impact of tumour-unrelated visceral surgery on the tumour-bearing organism and on the primary tumour itself is not yet fully understood. (2) Methods: We combined a murine model of orthotopically implanted adenocarcinoma of the pancreas with the model of surgically-induced immune dysfunction (SID). Mortality and general condition including body weight were observed over a period of 28 days. Tumour growth was analysed by MRI scans on days 8 and 27 following tumour implantation. On day 28, the immune cell populations in the blood and spleen as well as the serum cytokines were quantified. (3) Results: SID results in a significant deterioration of the general condition and a reduced increase in the body weight of tumour-bearing mice compared to the control groups, while mortality and tumour growth rate were not influenced. The numbers of spleen macrophages and neutrophils were increased in tumour-bearing animals following SID. Furthermore, both macrophage and neutrophil levels were increased in the peripheral blood. (4) Conclusions: The presented results might contribute to the basic understanding of the interaction of tumour and immune system and could contribute to new approaches to immunotherapeutic strategies.