【摘 要】
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The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages,and plays a critical role in regulating inflammatory response.Our previous work has shown its role in promoting the progression of non-small cell lung cance
【机 构】
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Department of Respiratory and Critical Care Medicine,Ren Ji Hospital,School of Medicine,Shanghai Jia
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The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages,and plays a critical role in regulating inflammatory response.Our previous work has shown its role in promoting the progression of non-small cell lung cancer(NSCLC),yet the mechanism remains unclear.Here,using Tgr5-knockout mice,we show that TGR5 is required for M2 polarization of tumor-associated macrophages(TAMs)and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+T cell suppression.Mechanistically,we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling.Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages.In NSCLC tissues from human patients,the expression of TGR5 is associated with the infiltration of TAMs.The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients.Together,this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC,high-lighting its potential as a target for TAMs-centric immunotherapy in NSCLC.
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