Immunological and Oxidative Stress Response in Relation to Abdominal Cancer Surgery

Background

The perioperative period is relatively short, but highly critical for cancer related survival. The surgical procedure results in release of tumor cells locally and in the blood, and induction of a surgical stress response (SSR). This leads to paralysis of the immune system, reduced clearance of cancer cells and optimal conditions for cancer cells to grow and metastasize(1).

Colorectal cancer (CRC) is the third most common cause of cancer in Denmark. In 2013, 4196 Danish patients were diagnosed with CRC(2) and current standard of care includes a tumour resection. However, even after an expected curative surgical tumour resection, 25-30% will have a relapse within 5 years after the primary procedure.

To improve the outcome after surgery for cancer, it is crucial to understand, in details, how SSR affects the immune response and how SSR affects the ability of cancer cells to grow and metastasize. By performing expression profiling of over 40.000 genes in whole blood before and after surgery, we will obtain a genetic signature of genes from circulating immune cells, including granulocytes, monocytes, B and T cells, dendritic cells, and platelets, which will enable us to see the exact impact surgery has on gene transcription of these immunological factors. By using this information, perioperative interventions can be performed to optimize the immunological response in the perioperative period, leading to reduced risk of cancer recurrence and consequently improved survival (3).

Surgical stress response (SSR) It is well known that a surgical procedure induces a disturbance of the immunological and inflammatory balance, causing a systemic inflammatory response (4), immune suppression (4,5) and excess reactive oxygen species (ROS) (6,7). Systemic inflammation promotes tumor growth (8), and in patients who have undergone potentially curative resection for colorectal cancer, the presence of a systemic inflammatory response predicts a poor outcome (3). The paralysis of the immune system includes reduced activity of NK cells and macrophages, both of which under normal circumstances protects against metastasis by eliminating disseminating tumor cells. Excessive ROS causes DNA damage, break down of extracellular matrix and elimination of cell-cell adhesions (5,6,7). In this way, surgery promotes optimal conditions for cancer cells to grow and metastasize in the post-operative phase. Recent research shows that immune cells and their invasion of the primary tumor correlates to the patient's prognosis, again suggesting that the immune response is important for inhibition of cancer growth(9,10). Detailed information of genetic changes in different factors of the immune response due to surgery remains unclear.