Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors

Nat Rev Cancer. 2006 Aug;6(8):613-25. doi: 10.1038/nrc1929.

Abstract

Cancer immunotherapy has been predominantly focused on biologically based intervention strategies. However, recent advances in the understanding of tumour-host interactions at the molecular level have revealed targets that might be amenable to intervention with small-molecule inhibitors. In particular, key effectors of tumoral immune escape have been identified that contribute to a dominant toleragenic state that is suspected of limiting the successful implementation of treatment strategies that rely on boosting immune function. Within the context of the pathophysiology of cancer-associated immune tolerance, this Review delineates potential molecular targets for therapeutic intervention and the progress that has been made in developing small-molecule inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Arginase / antagonists & inhibitors
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cytokines / antagonists & inhibitors
  • Humans
  • Immune Tolerance / drug effects*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Neoplasms / drug therapy
  • Neoplasms / immunology*
  • Neoplasms / physiopathology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Vascular Endothelial Growth Factors / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Vascular Endothelial Growth Factors
  • Nitric Oxide Synthase
  • Arginase