Surgical resection with curative intent is the mainstay of treatment for patients with solid malignancies. While lifesaving and necessary, a large majority of patients recur due to minimal residual disease present at the time of surgery. There is increasing mechanistic evidence from clinically relevant animal models and cancer patients to suggest that surgical resection negatively affects the host immune system leading to the proliferation of occult tumors. These immunosuppressive effects may explain for the high postoperative recurrence rates when surgery is used as a single treatment method.
We and others have shown that both innate and adaptive immunity is severely affected by surgical resection and this creates an immunosuppressive window of opportunity for the expansion of occult tumors and tumor escape. Specifically, we have demonstrated a severe, but reversible dysfunction of natural killer immune cell function in the postoperative period. The combined negative effects of malignant disease and surgery on the host immune system necessitate attempts at therapeutic immunomodulation during the perioperative period.
We are currently investigating the molecular and cellular mediators of surgery-induced immunosuppression, with an interest on tumor extrinsic natural killer and other immune cell interactions. Importantly, we are developing novel immunotherapeutic approaches for the perioperative period with a particular focus on the rational and sequential pairing of immunotherapies with surgical resection to prevent and reduce postoperative metastatic disease. We envisage that the protection of patients against perioperative tumor growth will be part of the accepted therapeutic paradigm in the near future.