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Innate immunity: Looking beyond T-cells in radiation and immunotherapy combinations.
McMahon, R A; D'Souza, C; Neeson, P J; Siva, S.
Afiliación
  • McMahon RA; Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia. Electronic address: Ryan.McMahon@petermac.org.
  • D'Souza C; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia; Cancer Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.
  • Neeson PJ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia; Cancer Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.
  • Siva S; Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia.
Neoplasia ; 46: 100940, 2023 Dec.
Article en En | MEDLINE | ID: mdl-37913654
ABSTRACT
Radiation therapy is an established and effective anti-cancer treatment modality. Extensive pre-clinical experimentation has demonstrated that the pro-inflammatory properties of irradiation may be synergistic with checkpoint immunotherapy. Radiation induces double-stranded DNA breaks (dsDNA). Sensing of the dsDNA activates the cGAS/STING pathway, producing Type 1 interferons essential to recruiting antigen-presenting cells (APCs). Radiation promotes cytotoxic CD8 T-cell recruitment by releasing tumour-associated antigens captured and cross-presented by surveying antigen-presenting cells. Radiation-induced vascular normalisation may further promote T-cell trafficking and drug delivery. Radiation is also immunosuppressive. Recruitment of regulatory T cells (Tregs) and innate cells such as myeloid-derived suppressive cells (m-MDSCs) all counteract the immunostimulatory properties of radiation. Many innate immune cell types operate at the interface of the adaptive immune response. Innate immune cells, such as m-MDSCs, can exert their immunosuppressive effects by expressing immune checkpoints such as PD-L1, further highlighting the potential of combined radiation and checkpoint immunotherapy. Several early-phase clinical studies investigating the combination of radiation and immunotherapy have been disappointing. A greater appreciation of radiotherapy's impact on the innate immune system is essential to optimise radioimmunotherapy combinations. This review will summarise the impact of radiotherapy on crucial cells of the innate immune system and vital immunosuppressive cytokines.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias / Antineoplásicos Límite: Humans Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article
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