A re-examination of the role of the acute phase protein response in innate cancer defence

Anti-cancer host defense mechanisms are traditionally considered to consist of tumor suppressor genes and immune surveillance by cells of the innate and adaptive immune systems. However, there is mounting evidence that components of the acute phase protein response (APPR), and, in particular, certain cationic host defense peptides (HDPs), also contribute to anti-cancer host defense. In a number of in vitro studies, certain HDPs have been shown to be cytotoxic to tumor cells either directly through cancer cell membrane destabilization and lysis or through the initiation of apoptosis in the cancer cell. In addition, many cancer cells elaborate the pro-inflammatory cytokine interleukin-6, which in turn produces an APPR that involves the release of HDPs. It is therefore possible that the release of pro-inflammatory cytokines by cancer cells initiates a poorly understood anti-tumor response by the host that involves HDP induction. We hypothesize that the APPR may form an important anti-cancer host defense response. This may be an important consideration in light of cancer treatments designed to decrease systemic inflammation. Blunting of the anti-cancer effect of the APPR may also contribute to the increased cancer rates seen in chronic immunosuppressive states.