协同刺激分子B7-H3与肿瘤

doi:10.3760/cma.j.issn.1673-422X.2017.11.011

摘要/Abstract

摘要： B7-H3分子是新近发现的协同刺激调节蛋白B7家族成员之一，其mRNA广泛表达于人类各种组织。B7-H3不仅能够作为共刺激或共抑制信号调节免疫反应，在免疫应答中发挥重要作用，而且可以参与肿瘤进展的非免疫调节。近年来研究发现B7H3在多种恶性肿瘤中异常表达并与患者预后不良、疾病进展密切相关，被认为是肿瘤早期诊断、预后判断指标以及临床治疗的分子靶点，但其中涉及的具体机制并不明确。同时，针对B7-H3分子免疫及基因治疗研究取得了一定成效。

关键词: 肿瘤, 协同刺激分子B7-H3

Abstract: B7-H3, a newly discovered co-stimulatory regulatory protein member of the B7 family. Its mRNA is ubiquitously expressed in a wide spectrum of tissues. As a co-stimulatory or co-inhibitory signal molecule which can regulate immune response, B7-H3 plays an important role in the immune system. Besides, B7-H3 can be also involved in cancer progression via nonimmunological. Recently, the aberrant expression of B7-H3 has been described in various malignancies, and significantly correlated with poor prognosis and cancer progression. Therefore, B7-H3 is considered as an early diagnostic and prognostic marker and therapeutic target for tumors, but the specific molecular mechanisms of B7-H3 regulation are poorly understood. The immune and gene therapy of tumor by target B7-H3 has made some progress.

Key words: Neoplasms, Co-stimulatory molecule B7-H3

朱晓雯，王晶，克晓燕. 协同刺激分子B7-H3与肿瘤[J]. 国际肿瘤学杂志, 2017, 44(11): 849-852.

朱晓雯，王晶，克晓燕. Co-stimulating molecule B7H3 and tumors[J]. Journal of International Oncology, 2017, 44(11): 849-852.

参考文献

［1］ Wang L, Kang FB, Shan BE. B7-H3mediated tumor immunology: friend or foe?［J］. Int J Cancer, 2014, 134(12): 2764-2771. DOI: 10.1002/ijc.28474. ［2］ Wang Z, Yang J, Zhu Y, et al. Differential expression of 2IgB7-H3 and 4IgB7-H3 in cancer cell lines and glioma tissues［J］. Oncol Lett, 2015, 10(4): 2204-2208. DOI: 10.3892/ol.2015.3611. ［3］ Duan H, Huang M. Genomewide identification and evolutionary analysis of B7-H3［J］. Int J Data Min Bioinform, 2012, 6(3): 292-303. ［4］ Feng P, Zhang H, Zhang Z, et al. The interaction of MMP2/B7H3 in human osteoporosis［J］. Clin Immunol, 2016, 162: 118124. DOI: 10.1016/j.clim.2015.11.009. ［5］ Chen X, Li Y, Blankson S, et al. B7H3 Augments inflammatory responses and exacerbates brain damage via amplifying NFκB p65 and MAPK p38 activation during experimental pneumococcal meningitis［J］. PLoS One, 2017, 12(1): e171146. DOI: 10.1371/journal.pone.0171146. ［6］ Ni L, Dong C. New checkpoints in cancer immunotherapy［J］. Immunol Rev, 2017, 276(1): 5265. DOI: 10.1111/imr.12524. ［7］ Hu Y, Lv X, Wu Y, et al. Expression of costimulatory molecule B7-H3 and its prognostic implications in human acute leukemia［J］. Hematology, 2015, 20(4): 187-195. DOI: 10.1179/1607845414Y.0000000186. ［8］ Fauci JM, Straughn JM Jr, Ferrone S, et al. A review of B7H3 and B7-H4 immune molecules and their role in ovarian cancer［J］. Gynecol Oncol, 2012, 127(2): 420-425. DOI: 10.1016/j.ygyno.2012.08.017. ［9］ Vigdorovich V, Ramagopal UA, LázárMolnár E, et al. Structure and T cell inhibition properties of B7 family member, B7H3［J］. Structure, 2013, 21(5): 707-717. DOI: 10.1016/j.str.2013.03.003. ［10］ Lim S, Liu H, Madeira DSL, et al. Immunoregulatory protein B7-H3 reprograms glucose metabolism in cancer cells by ROSmediated stabilization of HIF1 alpha［J］. Cancer Res, 2016, 76(8): 22312242. DOI: 10.1158/00085472.CAN151538. ［11］ Tabellini G, Benassi M, Marcenaro E, et al. Primitive neuroectodermal tumor in an ovarian cystic teratoma: natural killer and neuroblastoma cell analysis［J］. Case Rep Oncol, 2014, 7(1): 7078. DOI: 10.1159/000357802. ［12］ Janakiram M, Shah UA, Liu W, et al. The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7H3［J］. Immunol Rev, 2017, 276(1): 2639. DOI: 10.1111/imr.12521. ［13］ Veenstra RG, Flynn R, Kreymborg K, et al. B7H3 expression in donor T cells and host cells negatively regulates acute graftversushost disease lethality［J］. Blood, 2015, 125(21): 3335-3346. DOI: 10.1182/blood2014-09-603357. ［14］ Ueno T, Yeung MY, McGrath M, et al. Intact B7-H3 signaling promotes allograft prolongation through preferential suppression of Th1 effector responses［J］. Eur J Immunol, 2012, 42(9): 2343-2353. DOI: 10.1002/eji.201242501. ［15］ Ni L, Dong C. New checkpoints in cancer immunotherapy［J］. Immunol Rev, 2017, 276(1): 52-65. DOI: 10.1111/imr.12524. ［16］ Tekle C, Nygren MK, Chen YW, et al. B7H3 contributes to the metastatic capacity of melanoma cells by modulation of known metastasisassociated genes［J］. Int J Cancer, 2012, 130(10): 2282-2290. DOI: 10.1002/ijc.26238. ［17］ Luo D, Xiao H, Dong J, et al. B7H3 regulates lipid metabolism of lung cancer through SREBP1mediated expression of FASN［J］. Biochem Biophys Res Commun, 2017, 482(4): 1246-1251. DOI: 10.1016/j.bbrc.2016.12.021. ［18］ Fan TF, Deng WW, Bu LL, et al. B7H3 regulates migration and invasion in salivary gland adenoid cystic carcinoma via the JAK2/STAT3 signaling pathway［J］. Am J Transl Res, 2017, 9(3): 1369-1380. ［19］ Kreymborg K, Haak S, Murali R, et al. Ablation of B7H3 but not B7H4 results in highly increased tumor burden in a murine model of spontaneous prostate cancer［J］. Cancer Immunol Res, 2015, 3(8): 849-854. DOI: 10.1158/2326-6066.CIR-15-0100. ［20］ Lemke D, Pfenning PN, Sahm F, et al. Costimulatory protein 4IgB7H3 drives the malignant phenotype of glioblastoma by mediating immune escape and invasiveness［J］. Clin Cancer Res, 2012, 18(1): 105117. DOI: 10.1158/10780432.CCR110880. ［21］ Sun TW, Gao Q, Qiu SJ, et al. B7H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence［J］. Cancer Immunol Immunother, 2012, 61(11): 21712182. DOI: 10.1007/s0026201212785. ［22］ Benzon B, Zhao SG, Haffner MC, et al. Correlation of B7H3 with androgen receptor, immune pathways and poor outcome in prostate cancer: an expressionbased analysis［J］. Prostate Cancer Prostatic Dis, 2017, 20(1): 2835. DOI: 10.1038/pcan.2016.49. ［23］ Qin X, Zhang H, Ye D, et al. B7H3 is a new cancerspecific endothelial marker in clear cell renal cell carcinoma［J］. Onco Targets Ther, 2013, 6: 1667-1673. DOI: 10.2147/OTT.S53565. ［24］ Fauci JM, Straughn JM Jr, Ferrone S, et al. A review of B7H3 and B7H4 immune molecules and their role in ovarian cancer［J］. Gynecol Oncol, 2012, 127(2): 420-425. DOI: 10.1016/j.ygyno.2012.08.017. ［25］ Zhou Z, Luther N, Ibrahim GM, et al. B7H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma［J］. J Neurooncol, 2013, 111(3): 257-264. DOI: 10.1007/s11060-012-1021-2. ［26］ Loo D, Alderson RF, Chen FZ, et al. Development of an Fcenhanced antiB7H3 monoclonal antibody with potent antitumor activity［J］. Clin Cancer Res, 2012, 18(14): 38343845. DOI: 10.1158/10780432.CCR-12-0715. ［27］ Dai W, Shen G, Qiu J, et al. Aberrant expression of B7H3 in gastric adenocarcinoma promotes cancer cell metastasis［J］. Oncol Rep, 2014, 32(5): 2086-2092. DOI: 10.3892/or.2014.3405. ［28］ Zhang W, Wang J, Wang Y, et al. B7H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells［J］. Onco Targets Ther, 2015, 8: 1721-1733. DOI: 10.2147/OTT.S85272. ［29］ Nygren MK, Tekle C, Ingebrigtsen VA, et al. Identifying microRNAs regulating B7H3 in breast cancer: the clinical impact of microRNA29c［J］. Br J Cancer, 2014, 110(8): 2072-2080. DOI: 10.1038/bjc.2014.113. ［30］ Xie C, Liu D, Chen Q, et al. Soluble B7H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NFκB pathway［J］. Sci Rep, 2016, 6: 27528. DOI: 10.1038/srep27528. ［31］ Chen L, Zhang G, Sheng S, et al. Upregulation of soluble B7H3 in NSCLCderived malignant pleural effusion: a potential diagnostic biomarker correlated with NSCLC staging［J］. Clin Chim Acta, 2016, 457: 81-85. DOI: 10.1016/j.cca.2016.04.009.

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