The current state of
cancer treatment is still far from being satisfactory considering the strong impairment of patients' quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by
tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic
antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a
biological effect of ionizing radiation that occurs outside the irradiated field), the influence of
cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by
anticancer agents are the main topics of this presentation. It is widely accepted that
tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of
anticancer agents are able to amplify already expressed
tumor-associated
antigens (TAA). More importantly, other drugs, especially
triazenes, induce the appearance of new
tumor neoantigens (TNA), a phenomenon that we termed
drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with
drug-induced increase in
tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and
immunotherapies are interacting and cooperate in evoking the abscopal effect,
tumor xenogenization and ICD, paving the way for new and possibly successful approaches in
cancer therapy.