B7H5于口腔颌面头颈肿瘤免疫治疗中作为联合用药靶点的应用潜力探究

›› 2018, Vol. 38 ›› Issue (11): 1048-1052.

B7H5于口腔颌面头颈肿瘤免疫治疗中作为联合用药靶点的应用潜力探究

赵昊明,赵华强

山东大学口腔医学院

收稿日期:2018-01-23 修回日期:2018-03-07 出版日期:2018-11-28 发布日期:2018-11-30
通讯作者: 赵华强 E-mail:zhaohuaqiangsdkq@163.com
基金资助:
省自然科学基金面上项目

Application potential exploration of B7H5 used as drug combination target in the immunotherapy of oromaxillofacial head and neck tumor

hao ming zhao¹,huaqiang zhao

Received:2018-01-23 Revised:2018-03-07 Online:2018-11-28 Published:2018-11-30
Contact: huaqiang zhao E-mail:zhaohuaqiangsdkq@163.com

摘要/Abstract

摘要： ［摘要］利用负性调节因子（NCR）进行肿瘤免疫治疗是目前口腔头颈肿瘤研究的一大热点。临床试验证明，相对于化疗药物，抗负性调节因子靶向药的疗效更加显著且对机体的伤害性更小。但随着肿瘤耐药机制研究的日趋深入，发现了大量针对靶向药物的肿瘤耐药案例，因而临床越来越强调联合用药，以期在降低肿瘤耐药及细胞毒性的同时，保证足够的治疗效果。B7H5，又名VISTA，是B7-CD28家族成员之一，与负性调节因子CTLA-4、PD-1、PD-L1等存在极高的同源性，亦属于NCR家族。目前关于B7H5免疫抑制方面的机制仍尚未完全阐明，其分子结构提示可能成为一个理想的联合用药靶点。本文就关于B7H5分子在口腔颌面头颈肿瘤免疫治疗方面的研究现状作一综述。

关键词: B7H5(VISTA), 负性调节因子（NCR）, 抗肿瘤免疫治疗, 肿瘤免疫抑制微环境, 肿瘤免疫编译

Abstract: Utilization of negative checkpoint regulators (NCRs) for immunotherapy has garnered significant interest of oral head and neck tumor research. Compared to chemotherapy, the anti-NCRs targeted drugs are more effective and less harmful with the demonstration of clinical trials. However, with the research of tumor resistance mechanism becoming more and more intensive, myriad tumor resistance cases have appeared for targeted drugs. Therefore, more and more emphasis is focused on combination therapy in order to reduce the resistance and cytotoxicity, and to ensure adequate therapeutic effect. B7H5, also named VISTA (V-domain Ig-containing Suppressor of T cell Activation), is a member of B7-CD28, which has sky-high homology with negative checkpoint factors CTLA-4, PD-1, PD-L1, and is also a member of NCR. At present, the immunosupression mechanism of B7H5 has not been clarified, whose molecule may become an ideal drug combination target. The article reviews the research status of B7H5 molecule in the immunotherapy of oromaxilofacial head and neck tumor.

Key words: B7H5(VISTA), Negative Checkpoint Regulators（NCR）, Anti-tumor immunotherapy, Immunosuppressive tumor microenvironment (ISTME), Tumor immuno-editing

中图分类号:

R739.8

赵昊明赵华强. B7H5于口腔颌面头颈肿瘤免疫治疗中作为联合用药靶点的应用潜力探究[J]. , 2018, 38(11): 1048-1052.

hao ming zhao huaqiang zhao. Application potential exploration of B7H5 used as drug combination target in the immunotherapy of oromaxillofacial head and neck tumor [J]. , 2018, 38(11): 1048-1052.

参考文献

[1]Schreiber RD, Old LJ, Smyth MJ.Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion[J].Science, 2011, 331(6024):1565-1570
[2]Wang L, Rubinstein R, Lines JL, et al.VISTA,a novel mouse Ig superfamily ligand that negatively regulates T cell responses[J].J Exp Med, 2011, 208(3):577-592
[3]Couzin-Frankel J.Breakthrough of the year 2013Cancer immunotherapy[J].Science, 2013, 342(6165):1432-1433
[4] Kondo Y, Ohno T, Nishii N, et al.Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma[J]. Oral Oncol, 2016, 57: 54-60.
[5]张锐, 王智煜, 文孝婷, 等.肿瘤免疫抑制微环境对肿瘤免疫治疗作用的研究进展[J].实用肿瘤学杂志, 2016, 30(2):167-171
[6]Lindau D, Gielen P, Kroesen M, et al.The immunosuppressive tumour network: myeloid-derived suppressor cells,regulatory T cells and natural killer T cells[J].Immunology, 2013, 138(2):105-115
[7]Topalian SL, Drake CG, Pardoll DM.Immune checkpoint blockade: a common denominator approach to cancer therapy[J].Cancer Cell, 2015, 27(4):450-461
[8]Wolchok JD, Saenger Y.The mechanism of anti-CTLA-4 activity and the negative regulation of T-cell activation[J].Oncologist, 2008, 13(Suppl 4):2-9
[9]Chen L, Han X.Anti-PD-1PD-L1 therapy of human cancer: past,present,and future[J].J Clin Invest, 2015, 125(9):3384-3391
[10]Pardoll DM.The blockade of immune checkpoints in cancer immunotherapy[J].Nat Rev Cancer, 2012, 12(4):252-264
[11]Le Mercier I, Chen W, Lines JL, et al.VISTA Regulates the Development of Protective Antitumor Immunity[J].Cancer Res, 2014, 74(7):1933-1944
[12]Kwek SS, Kahn J, Greaney SK, et al.GM-CSF and ipilimumab therapy in metastatic melanoma: Clinical outcomes and immunologic responses[J].Oncoimmunology, 2016, 5(4):e1101204-
[13]Khoja L, Atenafu EG, Ye Q, et al.Real-world efficacy,toxicity and clinical management of ipilimumab treatment in metastatic melanoma[J].Oncol Lett, 2016, 11(2):1581-1585
[14]Ornstein MC, Rini BI.The safety and efficacy of nivolumab for the treatment of advanced renal cell carcinoma[J].Expert Rev Anticancer Ther, 2016, 16(6):577-584
[15]Gentzler R, Hall R, Kunk PR, et al.Beyond melanoma: inhibiting the PD-1PD-L1 pathway in solid tumors[J].Immunotherapy, 2016, 8(5):583-600
[16] Dempke WCM, Fenchel K, Uciechowski P, et al.Second- and third-generation drugs for immuno-oncology treatment-The more the better[J]. Eur J Cancer, 2017, 74: 55-72.
[17]Nowak EC, Lines JL, Varn FS, et al.Immunoregulatory functions of VISTA[J].Immunol Rev, 2017, 276(1):66-79
[18]Talmadge JE, Gabrilovich DI.History of myeloid-derived suppressor cells[J].Nat Rev Cancer, 2013, 13(10):739-752
[19]Youn JI, Nagaraj S, Collazo M, et al.Subsets of myeloid-derived suppressor cells in tumor-bearing mice[J].J Immunol, 2008, 181(8):5791-5802
[20]Youn J I, Collazo M, Shalova I N, et al.Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice[J].Journal of Leukocyte Biology, 2011, 91(1):167-181
[21]Haymaker C, Wu R, Bernatchez C, et al.PD-1 and BTLA and CD8(+) T-cell "exhaustion" in cancer: "Exercising" an alternative viewpoint[J].Oncoimmunology, 2012, 1(5):735-738
[22]Derré L, Rivals J P, Jandus C, et al.BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination[J].Journal of Clinical Investigation, 2010, 120(1):157-167
[23]Srivastava MK, Sinha P, Clements VK, et al.Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine[J].Cancer Res, 2010, 70(1):68-77
[24]Gabrilovich DI, Ostrand-Rosenberg S, Bronte V.Coordinated regulation of myeloid cells by tumours[J].Nat Rev Immunol, 2012, 12(4):253-268
[25]Nagaraj S, Gupta K, Pisarev V, et al.Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer[J].Nat Med, 2007, 13(7):828-835
[26]Hanson EM, Clements VK, Sinha P, et al.Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells[J].J Immunol, 2009, 183(2):937-944
[27]Molon B, Ugel S, Del Pozzo F, et al.Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells[J].J Exp Med, 2011, 208(10):1949-1962
[28]Noman MZ, Desantis G, Janji B, et al.PD-L1 is a novel direct target of HIF-1α,and its blockade under hypoxia enhanced MDSC-mediated T cell activation[J].J Exp Med, 2014, 211(5):781-790
[29]Kim K, Skora AD, Li Z, et al.Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells[J].Proc Natl Acad Sci USA, 2014, 111(32):11774-11779
[30]Bharaj P, Chahar HS, Alozie OK, et al.Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals[J].PLoS ONE, 2014, 9(10):e109103-
[31]Liu J, Yuan Y, Chen W, et al.Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses[J].Proc Natl Acad Sci USA, 2015, 112(21):6682-6687
[32]Twyman-Saint Victor C, Rech AJ, Maity A, et al.Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J].Nature, 2015, 520(7547):373-377
[33]Flies DB, Wang S, Xu H, et al.Cutting edge: A monoclonal antibody specific for the programmed death-1 homolog prevents graft-versus-host disease in mouse models[J].J Immunol, 2011, 187(4):1537-1541
[34]Lines JL, Pantazi E, Mak J, et al.VISTA is an immune checkpoint molecule for human T cells[J].Cancer Res, 2014, 74(7):1924-1932
[35]Radhakrishnan S, Nguyen LT, Ciric B, et al.B7-DCPD-L2 cross-linking induces NF-kappaB-dependent protection of dendritic cells from cell death[J].J Immunol, 2007, 178(3):1426-1432