title: Emerging role of tumor-associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma.
abstract: Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes recruited into the renal cell carcinoma (RCC) microenvironment. In response to inflammatory stimuli, macrophages undergo M1 (classical) or M2 (alternative) activation. M1 cells produce high levels of inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-12, IL-23 and IL-6, while M2 cells produce anti-inflammatory cytokines, such as IL-10, thus contributing to RCC-related immune dysfunction. The presence of extensive TAM infiltration in RCC microenvironment contributes to cancer progression and metastasis by stimulating angiogenesis, tumor growth, and cellular migration and invasion. Moreover, TAMs are involved in epithelial-mesenchymal transition of RCC cancer cells and in the development of tumor resistance to targeted agents. Interestingly, macrophage autophagy seems to play an important role in RCC. Based on this scenario, TAMs represent a promising and effective target for cancer therapy in RCC. Several strategies have been proposed to suppress TAM recruitment, to deplete their number, to switch M2 TAMs into antitumor M1 phenotype and to inhibit TAM-associated molecules. In this review, we summarize current data on the essential role of TAMs in RCC angiogenesis, invasion, impaired anti-tumor immune response and development of drug resistance, thus describing the emerging TAM-centered therapies for RCC patients.
authors.affiliation: Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, via Conca 71, 60126, Ancona, Italy, mattymo@alice.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.forename: Consuelo
authors.initials: C
authors.lastname: Amantini
authors.forename: Massimo
authors.initials: M
authors.lastname: Nabissi
authors.forename: Francesca
authors.initials: F
authors.lastname: Maines
authors.forename: Luciano
authors.initials: L
authors.lastname: Burattini
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D059016:Tumor Microenvironment