Antitumoral action of interferons and interleukins in combination with radiotherapy. Part 1: Immunologic basis

Background: During the Last 2 decades, cytokines such as interferons (IFN) have been used to modulate tumor response in radiotherapy. Initially, the focus was on antiviral and radiosensitizing effects of interferons but increasingly, the function of interferons and interleukins (IL) within the immune response to tumor cells is becoming important. Method: The cellular immune response toward tumor cells is reviewed. The role of cytokines in antigen presentation and activation of effector cells and their interactions with radiation are described. Preclinical strategies of the antitumor action of cytokines are presented and discussed based on the induction of IFN-gamma by IL-12. Results: Recent advances in immunology have demonstrated the importance of Local interactions between antigen-presenting cells (APC) and effector cells such as natural killer (NK) cells and T-lymphocytes for an effective immune reaction against tumors. Interferons stimulate such interactions, while IL-2 plays a central role in the activation of NK cells and T-lymphocytes. The interactions between APC and effector cells are suppressed by many tumors but can be stimulated by irradiation. Since systemic application of interferons is quite toxic, present strategies aim at Local expression, e.g., the induction of IFN-gamma expression in Th1 cells by IL-12. Conclusion: The improved understanding of immunologic mechanisms has emphasized the role of the cytokine network in the interaction between tumor cells and effector cells such as NK cells and T-lymphocytes. This opens new possibilities for the application of cytokines as biological response modifiers, which may eventually help widening the therapeutic window in radiotherapy.