Radiation dose, schedule and novel systemic targets for radio-immunotherapy combinations
Cet article examine les données actuelles concernant l'efficacité et la sécurité de traitements par immunothérapie pour réguler les effets immunomodulateurs induits par la radiothérapie
Immunotherapy combinations are being investigated to expand the benefit of immune- checkpoint blockade across many cancer types. Radiation combinations, in particular using stereotactic body radiotherapy (SBRT), are of keen interest due to underlying mechanistic rationale, safety, and availability as a standard of care in certain cancers. In addition to direct tumor cytotoxicity, radiation therapy has immunomodulatory effects such as induction of immunogenic cell death, enhancement of antigen presentation, expansion of the T cell receptor repertoire as well as recruitment and increased activity of tumor-specific effector CD8+ cells. Combinations of radiation with cytokines/chemokines and anti-programmed death 1 (PD1) and anti-cytotoxic-T-lymphocyte-antigen 4 (CTLA4) therapies have demonstrated safety and feasibility, as well as the potential to improve long term outcomes and possibly induce out of irradiated field or “abscopal” responses. Novel immuno-radiotherapy combinations represent a promising therapeutic approach to overcome radio-resistance and further enhance systemic immunotherapy. Potential benefits include reversing CD8+ T cell exhaustion, inhibiting myeloid-derived suppressor cells (MDSC) and reversing M2 macrophage polarization as well as decreasing levels of colony-stimulating-factor-1 (CSF-1) and transforming-growth factor-β (TGF- β). Here we discuss current data and mechanistic rationale for combining novel immunotherapy agents with radiation therapy.