Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors.
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.
Muller
Alexander J
AJ
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA. MullerA@MLHS.ORG
Scherle
Peggy A
PA
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001119:Arginase / Q000037:antagonists & inhibitors; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D042442:Vascular Endothelial Growth Factors; D019001:Nitric Oxide Synthase; D001119:Arginase