Abstract
FDA approval of the multitargeted, antiangiogenic tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib, and the serine and threonine mammalian target of rapamycin inhibitor, temsirolimus, has revolutionized the management of metastatic clear-cell renal-cell carcinoma (CC-RCC). The inability of these targeted therapies to provide durable complete responses, however, is a serious limiting factor to their clinical usefulness. Although immunotherapeutic approaches in advanced disease are increasingly regarded as a historical treatment paradigm, we propose that a fundamental understanding of immunobiology in CC-RCC can improve the selection of patients for high-dose intravenous interleukin 2 and facilitate the development of novel immunotherapeutic strategies. In our opinion, immunotherapeutic strategies have an important place in the management of advanced CC-RCC in the era of biological targeted therapy.
MeSH terms
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Angiogenesis Inhibitors / therapeutic use
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Antigens, Neoplasm / analysis
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Biomarkers, Tumor / analysis
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Cancer Vaccines / therapeutic use
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Carbonic Anhydrase IX
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Carbonic Anhydrases / analysis
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Carcinoma, Renal Cell / blood supply
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Carcinoma, Renal Cell / drug therapy
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Carcinoma, Renal Cell / immunology
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Carcinoma, Renal Cell / secondary*
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Carcinoma, Renal Cell / therapy
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Clinical Trials as Topic / statistics & numerical data
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Combined Modality Therapy
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Cytokines / therapeutic use
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Drug Delivery Systems
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Humans
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Immunoconjugates / therapeutic use
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Immunotherapy*
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Infusions, Intravenous
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Interferon-alpha / administration & dosage
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Interferon-alpha / therapeutic use*
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Interleukin-2 / administration & dosage
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Interleukin-2 / therapeutic use*
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Kidney Neoplasms / blood supply
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / immunology
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Kidney Neoplasms / pathology
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Kidney Neoplasms / therapy*
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Meta-Analysis as Topic
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Neoplasm Proteins / immunology
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Neoplasm Proteins / physiology
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Patient Selection
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Protein Kinase Inhibitors / therapeutic use
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
Substances
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Angiogenesis Inhibitors
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Antigens, Neoplasm
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Antineoplastic Agents
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Biomarkers, Tumor
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Cancer Vaccines
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Cytokines
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Immunoconjugates
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Interferon-alpha
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Interleukin-2
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Neoplasm Proteins
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Protein Kinase Inhibitors
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CA9 protein, human
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Carbonic Anhydrase IX
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Carbonic Anhydrases