Immune mechanisms mediating abscopal effects in radioimmunotherapy

Publication date: Available online 5 December 2018Source: Pharmacology & TherapeuticsAuthor(s): María E. Rodriguez-Ruiz, I. Rodriguez, Olwen Leaman, Fernando López Campos, Angel Montero, Antonio J. Conde, J.J. Aristu, Pedro Lara, Manuel Calvo Felipe, Ignacio MeleroAbstractRadiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the irradiated fields. However, ionizing radiation exerts multiple biological effects on both malignant and stromal cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. In the era of immunotherapy, interest in radiation-induced inflammation and cell death has considerably risen, since these mechanisms lead to profound changes in the systemic immune response against cancer antigens. Immunotherapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40, anti-CD40, anti-TGFβ), TLR-agonists, and adoptive T-cell therapy have been synergistically combined with radiotherapy in mouse models. Importantly, radiation and immunotherapy combinations do not only act against the irradiated tumor but also against distant non-irradiated metastases (abscopal effects). A series of clinical trials are exploring the beneficial effects of radioimmunotherapy combinations. The concepts of crosspriming of tumor neoantigens and immunogenic cell death are key elements underlying this combination efficacy. Proinflamatory changes in the vas...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research