Targeting of TAMs:can we be more clever than cancer cells?  

作　　者：Julia Kzhyshkowska Jiaxin Shen and Irina Larionova 

机构地区：[1]Department of Innate Immunity and Tolerance,Institute of Transfusion Medicine and Immunology,Mannheim Institute for Innate Immunoscience(MI3),Medical Faculty Mannheim,University of Heidelberg,Theodor-Kutzer-Ufer,1-3,68167 Mannheim,Germany [2]German Red Cross Blood Service Baden-Württemberg-Hessen,Friedrich-Ebert Str.107,68167 Mannheim,Germany [3]Laboratory of Translational Cellular and Molecular Biomedicine,National Research Tomsk State University,634050,Lenina av.36,Tomsk,Russia [4]Bashkir State Medical University of the Ministry of Health of Russia,450000,Teatralnaya Street,2a,Ufa,Russia [5]Department of Ultrasound in Medicine,The Second Affiliated Hospital of Zhejiang University School of Medicine,Zhejiang University,Hangzhou 310009,China [6]Laboratory of Molecular Therapy of Cancer,Cancer Research Institute,Tomsk National Research Medical Center,Russian Academy of Sciences,634009,Kooperativnyi st,Tomsk,Russia

出　　处：《Cellular & Molecular Immunology》2024年第12期1376-1409,共34页中国免疫学杂志(英文版)

基　　金：supported by the China Scholarship Council(No.202306320511);by the BSMU Strategic Academic Leadership Program PRIORITY-2030.

摘　　要：With increasing incidence and geography,cancer is one of the leading causes of death,reduced quality of life and disability worldwide.Principal progress in the development of new anticancer therapies,in improving the efficiency of immunotherapeutic tools,and in the personification of conventional therapies needs to consider cancer-specific and patient-specific programming of innate immunity.Intratumoral TAMs and their precursors,resident macrophages and monocytes,are principal regulators of tumor progression and therapy resistance.Our review summarizes the accumulated evidence for the subpopulations of TAMs and their increasing number of biomarkers,indicating their predictive value for the clinical parameters of carcinogenesis and therapy resistance,with a focus on solid cancers of non-infectious etiology.We present the state-of-the-art knowledge about the tumorsupporting functions of TAMs at all stages of tumor progression and highlight biomarkers,recently identified by single-cell and spatial analytical methods,that discriminate between tumor-promoting and tumor-inhibiting TAMs,where both subtypes express a combination of prototype M1 and M2 genes.Our review focuses on novel mechanisms involved in the crosstalk among epigenetic,signaling,transcriptional and metabolic pathways in TAMs.Particular attention has been given to the recently identified link between cancer cell metabolism and the epigenetic programming of TAMs by histone lactylation,which can be responsible for the unlimited protumoral programming of TAMs.Finally,we explain how TAMs interfere with currently used anticancer therapeutics and summarize the most advanced data from clinical trials,which we divide into four categories:inhibition of TAM survival and differentiation,inhibition of monocyte/TAM recruitment into tumors,functional reprogramming of TAMs,and genetic enhancement of macrophages.

关 键 词：EPIGENETIC Metabolism Scavenger receptor CYTOKINE Growth factor Angiogenesis Immunotherapy 

分 类 号：R730.5[医药卫生—肿瘤]