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dc.contributor.authorMaría E. Rodriguez-Ruiz, I. Rodriguez, Olwen Leaman, Fernando López Campos, Angel Montero, Antonio J. Conde, J.J. Aristu, Pedro Lara, Manuel Calvo Felipe, Ignacio Melero
dc.date.accessioned2024-01-18T09:05:15Z
dc.date.available2024-01-18T09:05:15Z
dc.date.issued2019
dc.identifier.citationPharmacol Ther . 2019 Apr:196:195-203. doi: 10.1016/j.pharmthera.2018.12.002. Epub 2018 Dec 5.es
dc.identifier.urihttp://hdl.handle.net/20.500.12020/1047
dc.description.abstractRadiotherapy 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 vasculature of the irradiated lesions and in the cellular composition of the leukocyte infiltrates in the tumor microenvironment contribute to raise or dampen cancer immunogenicity. It should be stressed that not all effects of radiotherapy favor antitumor immunity as there are counterbalancing mechanisms such as TGFβ, and VEGFs that inhibit the efficacy of the antitumor immune response, hence offering additional therapeutic targets to suppress. All in all, radiotherapy and immunotherapy are compatible and often synergistic approaches against cancer that jointly target irradiated and non-irradiated malignant lesions in the same patient.es
dc.language.isoenes
dc.titleImmune mechanisms mediating abscopal effects in radioimmunotherapyes
dc.typearticlees
dc.identifier.doihttps://doi.org/10.1016/j.pharmthera.2018.12.002
dc.journal.titlePharmacology and Therapeuticses
dc.page.initial195es
dc.page.final203es
dc.rights.accessRightsopenAccesses
dc.subject.areaCiencias Biomédicases


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