Immunological Mechanisms of Low and Ultra-Low Dose Cancer Chemotherapy.

Traditionally, anticancer chemotherapy has been generally considered to be strongly immunosuppressive. However, increasing evidence suggests that certain chemotherapeutic agents rely on the induction of antitumor immune responses, in both experimental animal models and patients with cancer. Many of these chemotherapeutic agents exert immunogenic effects via the induction and release of immunostimulatory "danger" signals from dying cancerous cells when used in low doses. New data suggests that several common chemotherapeutic agents may also display direct stimulating effects on immune cells even when applied in ultra-low concentrations (chemoimmunomodulation). Importantly, it is becoming clear that both immune effector cells and immune regulatory cells can be targeted by various chemotherapeutic agents to produce favorable antitumor immune responses. Therefore, utilizing cancer drugs to enhance host antitumor immunity should be considered a feasible therapeutic approach; and recent characterization of the immunomodulatory mechanisms of anticancer chemotherapy using both new and traditional cytotoxic agents suggests that combinations of these approaches with "classical" immunomodulatory agents could lead to a viable new therapeutic paradigm for the treatment of cancer.