Angiogenesis and Immunity in Renal Carcinoma: Can We Turn an Unhappy Relationship into a Happy Marriage?

Alessia Mennitto, Veronica Huber, Raffaele Ratta, Pierangela Sepe, Filippo de Braud, Giuseppe Procopio, Valentina Guadalupi, Mélanie Claps, Marco Stellato, Elena Daveri, Licia Rivoltini, Elena Verzoni

Research output: Contribution to journalArticlepeer-review


The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells' (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC.
Original languageEnglish
JournalJournal of Clinical Medicine
Issue number4
Publication statusPublished - Mar 1 2020


  • immunotherapy
  • metastatic renal cell carcinoma
  • angiogenesis
  • immune checkpoint inhibitors
  • immunomodulation
  • tyrosine-kinase inhibitors


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