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1、乳酸对炎症与肿瘤微环境中免疫反应的调节作用誓周文献阅读Lactate modulation of immune esponses in inflammatory versus tumour microenvironmentsMicheiangeio Certo Chin-Hsien Isai2. Valentina Pucino sr Ping-Chih Ho and Claudio Mauro r j-*E4冏叙血 Of肋她她口X Wd 口 皿 氐n 则 Sciences,乳馥对炎症与肿瘤微环境中免疫反应的调节作用Un 诞E伯 offiimfnoJTOm. flimwjw/firiffl.
2、UK-期刊：Nat Rev Immuno.IF/社科院分区；40.4/1 E发表时间：年8月除综述目的除肿瘤与免疫介导的炎症性疾病（IMIDs ）具有相似的代谢微环境， 如乏氧、乳酸和其它代谢中间产物水平升高、营养缺乏等，但两者却 存在一些截然对立的免疫特征，比如肿瘤微环境抑制免疫监测，而 IMIDs微环境则促进炎症反应。脂质代谢在激活巨噬细胞极化、T细胞分化等方面具有重要作用， 同时肿瘤细胞脂肪酸合成最重要的意义之一是改变肿瘤细胞的膜组成 和流动性，从而对化疗产生更强的抵抗力。免疫细胞中的 FAS 激活则 能降低肿瘤组织驻留的树突状细胞的免疫刺激能力。 该综述描述了乳酸调控免疫反应的机制，以
3、及在肿瘤和炎症性疾 病微环境中对乳酸截然不同的反应是如何形成的。GLUT1GLU1111 Migraiion乳酸在炎症性疾病微环境（关节炎滑膜）中的免疫调节作用Inflammatory mic noonvironment 1 pli T HypciMiA J. Mui应nt鼻l.ctarinSyncrviaL fibrohlfliEtTCA cyi-leSLC16A3Loetntcooceryl-CoAiPyruvnECilFttDEFiy, 1 | lmmuir-|iOtbiQidluL$il：Qry 4ff*hijIji at a（,” 1,1 曲配*1 ria kJ ajE i ilby
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7、苗:LDHA IM?俱加迂因运m TIL出TVEGl:OtARCTCCLS* ArM.JI pH inMirnrinicnl, R.-educ-sd CDla and iMMS就I CD14 e.KprSBlCHFl-Al ItmjI iun of GPRftl wd ifFiport vi* SLCilSAAdtytCaAi/ 0KaloHC1atekCl ItG Gutnnii.n| HypoxqI DifliffrwntiHtioni 上 II72 JlL-bXPNF1 Kjrtnine(Mrwir.tk 4HT-uiinour efllk慢性炎症过程。乳酸可介导炎症组织中 T 细胞运动
8、受抑伴随着糖酵解 的减少，促进CD4 T细胞增殖和向促炎症亚群的转换。3. 在肿瘤微环境中，来自癌细胞或基质细胞的质子偶联乳酸排在 酸性表型的保存中起着只至关重要的作用，这些乳酸通过调节TME来 促进肿瘤进展，包括侵袭、血管生成、生存信号、转移进展和逃避免 疫监视。4. 细胞外乳酸水平可被肿瘤等多种细胞感知，精细调节细胞行为 并强烈影响 TME 这些细胞的功能，支持肿瘤细胞的代谢适应，促进免 疫逃逸和肿瘤进展。乳酸在肿瘤微环境中的免疫调节作用仙谷Li” og列初记帆* Inhibition of Lactate- cIRuk Acidic pH ciwInonincrM. Rt-duced N
9、AaD a.-Bi La bi If tvT WEF arwIVEGFR； Lhrqh PAR如1 Cj-tohtic i fynction g 丄附 f Apcipt 口ti、HLT r Motilrty f Ancikgens rOXPJ-mediaieJ nepreuiam of MhrC end m*du 时祐 mMLDH SuttaMfd rmicid synthe-tis through ACCIhhibi* 亦创 NFATaftdNK|j46 QrllibilHMi1 cl inTUR. ikigniillingiFig* 2 I Lactate in the tumour mi
10、croenvironment. The tumour microenvironment (TME) is characterized by the presence of various cell typesH including tumouc stromal and immune cells, as well as blood vessels. In this meta bolically hcistite microenvironment, tumourcelh use most of the nutrients, th us effecting functions of the infi
11、ltrating immu nt? cells. Moreover &5 ci consequence of the Warburg effect, tumour cells secrete large amounts of lactate into the extracellular microenvironment, leading to acidosis* angiogenesis and immunosuppression. Indeed, lactate is reported to be one of tfiE most prominent mctiibolilcs uf the
12、TME that moduliitcs the mctabclrsm of in note and adaptive immu nc cells, inhibiting the activation jnd proliferation of CD8T ce Ils, natural kilter (N K) cells and dendritic cells. Lactate positively affects the CD4+CD2 5* regutatary I (Ttcy) cell metabolic nrnfilp oruihlirvi thoirnrin thp ;iririir IMP 薛nrl nnt
