Broomfield S et al. (2005) Partial, but not complete, tumor-debulking surgery promotes protective antitumor memory when combined with chemotherapy and adjuvant immunotherapy. Cancer Res 65: 7580–7584

Resection of advanced solid tumors is rarely successful because there is a high degree of local recurrence and growth of previously undetectable micrometastases. Postsurgical adjuvant therapy (immunotherapy or chemotherapy) used in an attempt to destroy these residual cancer cells has met with limited success. Because of this, many patients with extensive disease are not considered candidates for surgery. Results from a recent animal study, however, suggest that, rather than being detrimental, partial debulking of solid tumors might actually elicit beneficial anti-tumor memory if followed by combination adjuvant therapy.

In this study, mice inoculated with mesothelioma-based tumor cells underwent either tumor debulking surgery or complete resection followed by combination therapy of chemotherapy (gemcitabine) plus immunotherapy (anti-CD40), or followed by PBS vehicle alone. Complete resection plus combination therapy was curative in ∼80% of cases, but failed to elicit long-term, tumor-specific memory. By contrast, debulking followed by combination therapy resulted in a similar cure rate to complete resection, and also resulted in a memory response, implying that persistence of antigen in the form of chemotherapy-induced apoptotic tumor cells is required for the induction of long-term immunity during immunotherapy.

The authors conclude that their findings have clinical implications and where complete resection of the tumor is an option, combination therapy will be more effective if used in conjunction with tumor vaccination. If some tumor remains in situ, however, combination therapy has the potential to induce a long-lasting immunity against recurrence.