title: The potential of radiotherapy to enhance the efficacy of renal cell carcinoma therapy.
abstract: Renal cell carcinoma (RCC) is an immunogenic tumor, but uses several immune-suppressive mechanisms to shift the balance from tumor immune response toward tumor growth. Although RCC has traditionally been considered to be radiation resistant, recent evidence suggests that hypofractionated radiotherapy contributes to systemic antitumor immunity. Because the efficacy of antitumor immune responses depends on the complex balance between diverse immune cells and progressing tumor cells, radiotherapy alone is unlikely to induce persistent antitumor immunity. Therefore, the combination of radiotherapy with drugs having synergistic immunomodulatory properties holds great promise with the optimal timing and sequence of modalities depending on the agent used. We highlight the immunomodulatory properties of targeted therapies, such as tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors and vascular endothelial growth factor (VEGF) neutralizing antibodies, and will suggest a combination schedule with radiotherapy based on the available literature. We also address the combination of radiotherapy with innovative treatments in the field of immunotherapy.
authors.affiliation: Department of Radiation Oncology and Experimental Cancer Research; Ghent University Hospital ; Ghent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: De Wolf
authors.affiliation: Tumor Immunology Laboratory; Department of Pulmonary Medicine; Ghent University Hospital ; Ghent, Belgium.
authors.forename: Karim
authors.initials: K
authors.lastname: Vermaelen
authors.affiliation: Department of Radiation Oncology and Experimental Cancer Research; Ghent University Hospital ; Ghent, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: De Meerleer
authors.affiliation: Unit Immunoregulation and Mucosal Immunology; VIB Inflammation Research Center ; Ghent, Belgium ; GROUP-ID Consortium; Ghent University and University Hospital ; Ghent, Belgium ; Department of Respiratory Medicine; Ghent University ; Ghent, Belgium ; Department of Pulmonary Medicine; Erasmus MC ; Rotterdam, The Netherlands.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Department of Radiation Oncology and Experimental Cancer Research; Ghent University Hospital ; Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
keywords: antitumor immunity; immunotherapy; radiotherapy; renal cell carcinoma; targeted therapy; treatment combination