Atypical chemokine receptors in cancer: friends or foes?

摘要

Thechemokinesystemisafundamentalcomponentofcancer‐relatedinflammationinvolvedinallstagesofcancerdevelopment.Itcontrolsnotonlyleukocyteinfiltrationinprimarytumorsbutalsoangiogenesis,cancercellproliferation,andmigrationtometastaticsites.Atypicalchemokinereceptorsareanew,emergingclassofregulatorsofthechemokinesystem.Theycontrolchemokinebioavailabilitybyscavenging,transporting,orstoringchemokines.Theycanalsoregulatetheactivityofcanonicalchemokinereceptorswithwhichtheysharetheligandsbyformingheterodimersorbymodulatingtheirexpressionlevelsorsignalingactivity.Here,wesummarizerecentresultsabouttheroleofthesereceptors(atypicalchemokinereceptor1/Duffyantigenreceptorforchemokine,atypicalchemokinereceptor2/D6,atypicalchemokinereceptor3/CXC‐chemokinereceptor7,andatypicalchemokinereceptor4/CC‐chemokinereceptor‐like1)onthetumorigenesisprocess,indicatingthattheireffectsarestrictlydependentonthecelltypeonwhichtheyareexpressedandontheircoexpressionwithotherchemokinereceptors.Indeed,atypicalchemokinereceptorsinhibittumorgrowthandprogressionthroughtheiractivityasnegativeregulatorsofchemokinebioavailability,whereas,onthecontrary,theycanpromotetumorigenesiswhentheyregulatethesignalingofotherchemokinereceptors,suchasCXC‐chemokinereceptor4.Thus,atypicalchemokinereceptorsarekeycomponentsoftheregulatorynetworkofinflammationandimmunityincancerandmayhaveamajoreffectonanti‐inflammatoryandimmunotherapeuticstrategies...