To promote the ability of patients to eliminate or control residual disease following primary tumor excision, we sought to potentiate anti-metastatic immune mechanisms during the critical perioperative period. This approach is rarely used perioperatively given contraindications to surgery. Thus, we adopted novel immune-stimulating that are known to have minimal adverse effects agents (e.g., activating TLR9 using CpG-C), and studied them during the critical perioperative period. Outcomes indicate marked improvements in long-term cancer outcomes in several models of cancer metastasis, specifically using CpG-C to prevent liver metastasis of colorectal cancer, and lung metastasis of various malignancies.

We also found that psychological stress jeopardizes the efficacy of immune stimulation and we are currently testing prophylactic pharmacological approaches to overcome such effects that are expected in the stressful clinical setting in cancer patients. Last, in order to protect activated immunocytes from the immune suppressive effects of surgery, we are using a combined perioperative “anti-stress immune-stimulatory” approach, combining CpG-C use withblockade of CAs and PGs signalling during surgery, aiming to devise multi-factorial anti-metastatic perioperative treatment without adverse effects. Most importantly, we are now conducting several translational studies in preparation for employing this integrated approach in cancer patients in future clinical trials.