Current opinion in oncology
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Antigens recognized by T cells in tumors include differentiation antigens, overexpressed antigens, cancer-testis, and mutated tumor neoantigens. Ionizing radiation causes damage to multiple biomolecules by direct energy deposition or by generation of free radicals, leading to cell death when the damage cannot be repaired. Tumor cell death induced by radiation will generate specific molecular signals that are sensed by antigen-presenting cells and stimulate their maturation and ability to cross-present tumor-derived antigens to T cells. Immunogenic cell death will complement the activity of immune checkpoint inhibitors. We will provide the emerging information coming from preclinical and clinical testing about the combinations of immunotherapies and radiotherapy. ⋯ Radiation therapy is confirmed to be a sensitizer of tumors to immune checkpoint inhibitors in clinical trials, and its application will be easy to implement and widespread. Conversely, many issues need to be addressed before radiotherapy can become such a valid immunogenic tool. An area of increasing importance will be the development of suitable biomarkers that will be able to reliably assess 'immunogenic tumor cell death', immune effector stimulation, and adaptive immunity. Such an immune profile of biomarkers will aid in searching for an optimal combination of radiotherapy and immunomodulation and allows patient selection and response prediction.
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In this review, we focus on the recent findings and future challenges in cancer treatment with immune checkpoint inhibitors. ⋯ The main challenge for the near future will be to predict efficacy of immune checkpoint blockade and to predict and prevent immune-related adverse events. More research should be done in order to find potential biomarkers that predict treatment response and/or toxicity; the optimal administration route, dosage, and frequency; and possible combinations of therapies that have an added or synergetic effect.