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.
Oncoimmunology. 2015 May 27*** epublish ***
Katrien De Wolf, Karim Vermaelen, Gert De Meerleer, Bart N Lambrecht, Piet Ost
Department of Radiation Oncology and Experimental Cancer Research; Ghent University Hospital ; Ghent, Belgium. , Tumor Immunology Laboratory; Department of Pulmonary Medicine; Ghent University Hospital ; Ghent, Belgium. , Department of Radiation Oncology and Experimental Cancer Research; Ghent University Hospital ; Ghent, Belgium. , 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. , Department of Radiation Oncology and Experimental Cancer Research; Ghent University Hospital ; Ghent, Belgium.