Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti-melanoma immune response

Int J Cancer. 2017 Feb 15;140(4):747-755. doi: 10.1002/ijc.30422. Epub 2016 Oct 22.


Melanoma is a highly lethal cutaneous tumor, killing affected patients through development of multiple poorly immunogenic metastases. Suboptimal activation of immune system by melanoma cells is often due to molecular modifications occurring during tumor progression that prevent efficient recognition of melanoma cells by immune effectors. Statins are HMG-CoA reductase inhibitors, which block the mevalonate synthesis pathway, used by millions of people as hypocholesterolemic agents in cardiovascular and cerebrovascular diseases. They are also known to inhibit Rho GTPase activation and Rho dependent signaling pathways. Rho GTPases are regarded as molecular switches that regulate a wide spectrum of cellular functions and their dysfunction has been characterized in various oncogenic process notably in melanoma progression. Moreover, these molecules can modulate the immune response. Since 10 years we have demonstrated that Statins and other Rho GTPases inhibitors are critical regulators of molecules involved in adaptive and innate anti-melanoma immune response. In this review we summarize our major observations demonstrating that these pharmacological agents stimulate melanoma immunogenicity and suggest a potential use of these molecules to promote anti-melanoma immune response.

Keywords: Rho GTPases; immunotherapy; melanoma; protein prenylation; statins.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Disease Progression
  • Enzyme Activation / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Immunity, Innate / drug effects
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / immunology
  • Mevalonic Acid / metabolism
  • Mice
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / physiology
  • Protein Prenylation / drug effects*
  • Signal Transduction / drug effects
  • rho GTP-Binding Proteins / antagonists & inhibitors*
  • rho GTP-Binding Proteins / physiology


  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Neoplasm Proteins
  • rho GTP-Binding Proteins
  • Mevalonic Acid