陈永俊;马雁冰;

• 1:中国医学科学院北京协和医学院医学生物学研究所

摘要(Abstract)：

白细胞介素-33(interleukin-33,IL-33)组成性表达于内皮细胞、成纤维细胞、上皮细胞等非造血细胞上,在基质细胞上可诱导性表达,其在病毒感染、自身免疫病、伤口愈合和纤维化中发挥重要作用。IL-33作为调节机体免疫的重要细胞因子之一,除对Th1和Th2型免疫具有激活和活性维持作用外,还能募集激活免疫抑制性细胞,反向调节机体免疫,保持免疫系统的稳态。IL-33在肿瘤免疫中具有双重作用,可能与肿瘤的组织起源、IL-33的剂量、肿瘤微环境、IL-33的来源等有关,IL-33在不同肿瘤免疫中的作用机制不同。本文就IL-33的功能及其在肿瘤免疫中的作用进行综述。

关键词(KeyWords)： 白细胞介素-33;肿瘤免疫;作用机制

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目（81773270）;; 云南省应用基础研究重点项目（2016FA049）

作者(Authors): 陈永俊;马雁冰;

DOI: 10.13200/j.cnki.cjb.003456

参考文献(References)：

• [1]TAKATORI H,MAKITA S,ITO T,et al.Regulatory mechanisms of IL-33-ST2-mediated allergic inflammation[J].Front Immunol,2018,9:2004.
• [2]LU B,YANG M,WANG Q.Interleukin-33 in tumorigenesis,tumor immune evasion,and cancer immunotherapy[J].J Mol Med(Berl),2016,94(5):535-543.
• [3]ERCOLANO G,FALQUET M,VANONI G,et al.ILC2s:New actors in tumor immunity[J].Front Immunol,2019,10:2801.
• [4]TANG X,WU F,FAN J,et al.Posttranscriptional regulation of interleukin-33 expression by micro RNA-200 in bronchial asthma[J].Mol Ther,2018,26(7):1808-1817.
• [5]XIANG Y,EYERS F,HERBERT C,et al.Micro RNA-487b is a negative regulator of macrophage activation by targeting IL-33production[J].J Immunol,2016,196(8):3421-3428.
• [6]LUTHI A U,CULLEN S P,MCNEELA E A,et al.Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases[J].Immunity,2009,31(1):84-98.
• [7]EISSMANN M F,DIJKSTRA C,JARNICKI A,et al.IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization[J].Nat Commun,2019,10(1):2735.
• [8]QI L,ZHANG Q,MIAO Y,et al.Interleukin-33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development[J].Int J Cancer,2020,146(5):1421-1434.
• [9]DOMINGUEZ D,YE C,GENG Z,et al.Exogenous IL-33restores dendritic cell activation and maturation in established cancer[J].J Immunol,2017,198(3):1365-1375.
• [10]PEINE M,MAREK R M,LOHNING M.IL-33 in T cell differentiation,function,and immune homeostasis[J].Trends Immunol,2016,37(5):321-333.
• [11]YANG S,TANG Y Y.Pivotal effects of FOXP3 in modulating immune response[J].Immunol J,2016(3):262.(in Chinese）杨爽，汤玉瑜.FOXP3在调节免疫应答中的作用[J].免疫学杂志，2016(3):262.
• [12]LI B,SAMANTA A,SONG X,et al.FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression[J].Proc Natl Acad Sci USA,2007,104(11):4571-4576.
• [13]KUNDU J K,SURH Y J.Inflammation:gearing the journey to cancer[J].Mutat Res,2008,659(1-2):15-30.
• [14]SHAO D,PERROS F,CARAMORI G,et al.Nuclear IL-33regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension[J].Biochem Biophys Res Commun,2014,451(1):8-14.
• [15]AMERI A H,MORADI TUCHAYI S,ZAALBERG A,et al.IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation[J].Proc Natl Acad Sci USA,2019,116(7):2646-2651.
• [16]ZHOU Q,WU X,WANG X,et al.The reciprocal interaction between tumor cells and activated fibroblasts mediated by TNF-α/IL-33/ST2L signaling promotes gastric cancer metastasis[J].Oncogene,2020,39(7):1414-1428.
• [17]LIN L,LI Y,LIU M,et al.The Interleukin-33/ST2 axis promotes glioma mesenchymal transition,stemness and TMZresistance via JNK activation[J].Aging,2020,12(2):1685-1703.
• [18]GRIESENAUER B,PACZESNY S.The ST2/IL-33 axis in immune cells during inflammatory diseases[J].Front Immunol,2017,8:475.
• [19]FENG X,LIU H,CHU X,et al.Recombinant virus-like particles presenting IL-33 successfully modify the tumor microenvironment and facilitate antitumor immunity in a model of breast cancer[J].Acta Biomater,2019,100:316-325.
• [20]XIAO P,WAN X,CUI B,et al.Interleukin 33 in tumor microenvironment is crucial for the accumulation and function of myeloid-derived suppressor cells[J].Oncoimmunology,2016,5(1):e1063772.
• [21]LIU J,WANG W,WANG L,et al.IL-33 initiates vascular remodelling in hypoxic pulmonary hypertension by up-regulating HIF-1αand VEGF expression in vascular endothelial cells[J].EBio Medicine,2018,33:196-210.
• [22]ZHANG J F,WANG P,YAN Y J,et al.IL?33 enhances glioma cell migration and invasion by upregulation of MMP2and MMP9 via the ST2-NF-κB pathway[J].Oncol Rep,2017,38(4):2033-2042.
• [23]BOURGEOIS E,VAN L P,SAMSON M,et al.The pro-Th2cytokine IL-33 directly interacts with invariant NKT and NKcells to induce IFN-gamma production[J].Eu J Immunol,2009,39(4):1046-1055.
• [24]MOUSSION C,ORTEGA N,GIRARD J P.The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo:a novel′alarmin′[J].PLo S One,2008,3(10):e3331.
• [25]SARANCHOVA I,HAN J,HUANG H,et al.Discovery of a metastatic immune escape mechanism initiated by the loss of expression of the tumour biomarker interleukin-33[J].Sci Rep,2016,6:30555.
• [26]GAO K,LI X,ZHANG L,et al.Transgenic expression of IL-33 activates CD8 (+) T cells and NK cells and inhibits tumor growth and metastasis in mice[J].Cancer Lett,2013,335(2):463-471.
• [27]ANDREONE S,SPADARO F,BUCCIONE C,et al.IL-33promotes CD11b/CD18-mediated adhesion of eosinophils to cancer cells and synapse-polarized degranulation leading to tumor cell killing[J].Cancers(Basel),2019,11(11):1664.
• [28]AKIMOTO M,HAYASHI J I,NAKAE S,et al.Interleukin-33enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer[J].Cell Death Dis,2016,7(1):e2057.
• [29]CUI G,YUAN A,PANG Z,et al.Contribution of IL-33 to the pathogenesis of colorectal cancer[J].Front Oncol,2018,8:561.
• [30]MEYER A R,GOLDENRING J R.Injury,repair,inflammation and metaplasia in the stomach[J].J Physiol,2018,596(17):3861-3867.
• [31]BONILLA W V,FRHLICH A,SENN K,et al.The alarmin interleukin-33 drives protective antiviral CD8 T cell responses[J].Science,2012,335(6071):984-989.
• [32]SLEDZINSKA A,VILA DE MUCHA M,BERGERHOFF K,et al.Regulatory T cells restrain interleukin-2-and blimp-1-dependent acquisition of cytotoxic function by CD4 (+) T cells[J].Immunity,2020,52(1):151-166.e156.
• [33]MORALES DEL VALLE C,MAXWELL J R,XU M M,et al.Costimulation induces CD4 T cell antitumor immunity via an innate-like mechanism[J].Cell Rep,2019,27 (5):1434-1445.e1433.
• [34]JACKAMAN C,DYE D E,NELSON D J.IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice[J].Age(Dordr),2014,36(3):9655.