Cabozantinib (XL-184) is a multitarget tyrosine kinase inhibitor (TKI) targeting receptor tyrosine kinases (RTKs) involved in oncogenesis and angiogenesis. It is currently the standard therapy for medullary thyroid cancer (MTC), metastatic renal cell carcinoma (mRCC), and hepatocellular carcinoma (HCC). Combination of Cabozantinib with immunotherapy is now a standard treatment in metastatic renal cancer, and its efficacy is being tested in ongoing clinical trial in prostate cancer patients. Here, we report that Cabozantinib may exert an immunostimulatory role by inducing immunogenic stress of prostate cancer cells and directly modulating dendritic cells (DCs). Cabozantinib treatment arrested the cell cycle and triggered immunogenic cell death (ICD) in prostate cancer cells in vitro. Cabozantinib had a direct effect on DCs by the down-modulation of β-catenin and change in migratory and costimulatory phenotype of the DCs. These results may suggest possible immunomodulatory effects induced by Cabozantinib that could be exploited to optimize patient-tailored immunotherapeutic treatments.

Immunogenic cell death and immunomodulatory effects of cabozantinib / Scirocchi, Fabio; Napoletano, Chiara; Pace, Angelica; Rahimi Koshkaki, Hassan; Di Filippo, Alessandra; Zizzari, Ilaria Grazia; Nuti, Marianna; Rughetti, Aurelia. - In: FRONTIERS IN ONCOLOGY. - ISSN 2234-943X. - 11:(2021). [10.3389/fonc.2021.755433]

Immunogenic cell death and immunomodulatory effects of cabozantinib

Scirocchi, Fabio;Napoletano, Chiara;Pace, Angelica;Rahimi Koshkaki, Hassan;Di Filippo, Alessandra;Zizzari, Ilaria Grazia;Nuti, Marianna;Rughetti, Aurelia
2021

Abstract

Cabozantinib (XL-184) is a multitarget tyrosine kinase inhibitor (TKI) targeting receptor tyrosine kinases (RTKs) involved in oncogenesis and angiogenesis. It is currently the standard therapy for medullary thyroid cancer (MTC), metastatic renal cell carcinoma (mRCC), and hepatocellular carcinoma (HCC). Combination of Cabozantinib with immunotherapy is now a standard treatment in metastatic renal cancer, and its efficacy is being tested in ongoing clinical trial in prostate cancer patients. Here, we report that Cabozantinib may exert an immunostimulatory role by inducing immunogenic stress of prostate cancer cells and directly modulating dendritic cells (DCs). Cabozantinib treatment arrested the cell cycle and triggered immunogenic cell death (ICD) in prostate cancer cells in vitro. Cabozantinib had a direct effect on DCs by the down-modulation of β-catenin and change in migratory and costimulatory phenotype of the DCs. These results may suggest possible immunomodulatory effects induced by Cabozantinib that could be exploited to optimize patient-tailored immunotherapeutic treatments.
2021
cabozantinib; immunogenic cell death (ICD); prostate cancer; dendritic cell (DC); TKI (tyrosine kinase inhibitors); extracellular vesicle (EV); HMGB1; immunotherapy
01 Pubblicazione su rivista::01a Articolo in rivista
Immunogenic cell death and immunomodulatory effects of cabozantinib / Scirocchi, Fabio; Napoletano, Chiara; Pace, Angelica; Rahimi Koshkaki, Hassan; Di Filippo, Alessandra; Zizzari, Ilaria Grazia; Nuti, Marianna; Rughetti, Aurelia. - In: FRONTIERS IN ONCOLOGY. - ISSN 2234-943X. - 11:(2021). [10.3389/fonc.2021.755433]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1581503
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