title: Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR-TKIs and mTOR inhibitor.
abstract: Angiogenesis and immunosuppression work hand-in-hand in the renal cell carcinoma (RCC) microenvironment. Tumor growth is associated with impaired antitumor immune response in RCC, which involves T cells, natural killer cells, dendritic cells (DCs) and macrophages. Vascular endothelial growth factor receptor (VEGFR), such as sorafenib, sunitinib, pazopanib and axitinib, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus and everolimus, do exert both antiangiogenic and immunomodulatory functions. Indeed, these agents affect neutrophil migration, as well as T lymphocyte-DC cross-talk, DC maturation and immune cell metabolism and reactivity. In this review, we overview the essential role of innate and adaptive immune response in RCC proliferation, invasion and metastasis and the relationship between tumor-associated immune cells and the response to targeted agents approved for the treatment of metastatic RCC.
authors.affiliation: Medical Oncology AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Consuelo
authors.initials: C
authors.lastname: Amantini
authors.forename: Luciano
authors.initials: L
authors.lastname: Burattini
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007680:Kidney Neoplasms / Q000276:immunology*; D009361:Neoplasm Invasiveness / Q000276:immunology; D009362:Neoplasm Metastasis / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000276:immunology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases
keywords: immune cells; immunotherapy; natural and adaptive immunity; renal cell carcinoma; targeted therapy