Implications of metabolism-driven myeloid dysfunctions in cancer therapy  

作　　者：Laura Strauss Valentina Guarneri Alessandra Gennari Antonio Sica 

机构地区：[1]Department of Immunopharmacology and Immuno Oncology,EMD Serono Research&Development Institute,Inc.,80119545A Middlesex Turnpike,Billerica,MA 01821,USA [2]Department of Surgery,Oncology and Gastroenterology,University of Padova,Padova,Italy [3]Veneto Institute of Oncology-IRCCS,Padua,Italy,Padova,Italy [4]Division of Oncology,Department of Translational Medicine,University of Eastern Piedmont,Novara,Italy [5]Department of Pharmaceutical Sciences,University of Eastern Piedmont,A.Avogadro,via Bovio 6,Novara,Italy [6]Humanitas Clinical and Research Center,IRCCS,Via Manzoni 56,Rozzano,Milan,Italy

出　　处：《Cellular & Molecular Immunology》2021年第4期829-841,共13页中国免疫学杂志（英文版）

基　　金：supported by the Associazione Italiana per la Ricerca sul Cancro(AIRC)(IG number 19885 to A.S.);AIRC 5x1000(number 22757);Fondazione Cariplo,and Ministero Universita’Ricerca(MIUR)(project:2017BA9LM5_001);Associazione"Augusto per la Vita",Novellara(RE)and Associazione"Medicine Rocks",Milano.

摘　　要：Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid responses.In chronic inflammatory states,including cancer,this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils,macrophages,and dendritic cells(DCs),thus giving rise to a decline in the antitumor effector lymphoid response.Cancer-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors,resulting in unresolved and chronic inflammation.This pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool,which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor site.Therefore,persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer,as well as to the severity of a broad range of diseases,including metabolic syndrome and autoimmune and infectious diseases.The aims of this review are to(1)define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients,(2)discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes,and(3)explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor immunity.We propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects(irAEs)for current therapeutic strategies,including immune checkpoint inhibitor(ICI)therapy.

关 键 词：MYELOPOIESIS Tumor-associated macrophages Myeloid-derived suppressor cells METABOLISM Cancer therapy 

分 类 号：R733[医药卫生—肿瘤]