B7家族成员B7H6在肿瘤中的研究进展
Research Progress of B7H6, a Member of B7 Family, in Tumors
DOI: 10.12677/ACM.2022.127887, PDF,   
作者: 李德勤:滨州医学院第二临床医学院,山东 烟台;青岛大学附属烟台毓璜顶医院,肿瘤内一科,山东 烟台;陈 剑*:青岛大学附属烟台毓璜顶医院,肿瘤内一科,山东 烟台
关键词: B7H6Nkp30癌症免疫治疗B7H6 Nkp30 Cancer Immunotherapy
摘要: B7H6又称NCR3LG1,是NK细胞表面受体NKp30的配体。NK细胞是先天免疫细胞,在识别和杀死肿瘤细胞方面发挥着关键作用。B7H6在不同类型的癌症中表达,并且与预后良好或不良相关。B7H6通过调节肿瘤生物学行为发挥多方面的作用。目前B7H6可能成为免疫治疗的关键潜在靶点。
Abstract: B7H6, also known as NCR3LG1, is the ligand of natural killer cell surface receptor NKp30. NK cells are innate immune cells that play a key role in recognizing and killing tumor cells. B7H6 expresses in different types of human cancer, and has been associated with either good or poor prognosis. B7H6 plays a multifaceted role by modulating various events of tumor biology. B7H6 is now recog-nized as a potential and critical target to immunotherapy.
文章引用:李德勤, 陈剑. B7家族成员B7H6在肿瘤中的研究进展[J]. 临床医学进展, 2022, 12(7): 6149-6155. https://doi.org/10.12677/ACM.2022.127887

参考文献

[1] Pazina, T., Shemesh, A., Brusilovsky, M., Porgador, A. and Campbell, K.S. (2017) Regulation of the Functions of Nat-ural Cytotoxicity Receptors by Interactions with Diverse Ligands and Alterations in Splice Variant Expression. Frontiers in Immunology, 8, Article No. 369. [Google Scholar] [CrossRef] [PubMed]
[2] Shimasaki, N., Jain, A. and Campana, D. (2020) NK Cells for Cancer Immunotherapy. Nature Reviews Drug Discovery, 19, 200-218. [Google Scholar] [CrossRef] [PubMed]
[3] Souza-Fonseca-Guimaraes, F., Cursons, J. and Huntington, N.D. (2019) The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy. Trends in Immunology, 40, 142-158. [Google Scholar] [CrossRef] [PubMed]
[4] Wang, B., Ran, Z., Liu, M. and Ou, Y. (2019) Prognostic Significance of Potential Immune Checkpoint Member HHLA2 in Human Tumors: A Comprehensive Analysis. Fron-tiers in Immunology, 10, Article No.1573. [Google Scholar] [CrossRef] [PubMed]
[5] Upadhaya, S., Neftelino, S.T., Hodge, J.P., Oliva, C., Campbell, J.R. and Yu, J.X. (2021) Combinations Take Centre Stage in PD1/PDL1 Inhibitor Clinical Trials. Nature Reviews Drug Discovery, 20, 168-169. [Google Scholar] [CrossRef] [PubMed]
[6] Nagai, S. and Azuma, M. (2019) The CD28-B7 Family of Co-Signaling Molecules. In: Azuma, M. and Yagita, H., Eds., Co-Signal Molecules in T Cell Activation, Vol. 1189, Springer, Singapore, 25-51. [Google Scholar] [CrossRef] [PubMed]
[7] Brandt, C.S., Baratin, M., Yi, E.C., Kennedy, J., Gao, Z., Fox, B., Haldeman, B., Ostrander, C.D., Kaifu, T., Chabannon, C., Moretta, A., West, R., Xu, W., Vivier, E. and Levin, S.D. (2009) The B7 Family Member B7-H6 Is a Tumor Cell Ligand for the Activating Natural Killer Cell Receptor NKp30 in Humans. Journal of Experimental Medicine, 206, 1495-1503. [Google Scholar] [CrossRef] [PubMed]
[8] Rusakiewicz, S., Perier, A., Semeraro, M., Pitt, J.M., Pogge Von Strandmann, E., Reiners, K.S., Aspeslagh, S., Pipéroglou, C., Vély, F., Ivagnes, A., Jegou, S., Halama, N., Chaigneau, L., Validire, P., Christidis, C., Perniceni, T., Landi, B., Berger, A., Isambert, N., Domont, J., Bonvalot, S., Terrier, P., Adam, J., Coindre, J.M., Emile, J.F., Poirier-Colame, V., Chaba, K., Rocha, B., Caignard, A., Toubert, A., Enot, D., Koch, J., Marabelle, A., Lambert, M., Caillat-Zucman, S., Leyvraz, S., Auclair, C., Vivier, E., Eggermont, A., Borg, C., Blay, J.Y., Le Cesne, A., Mir, O. and Zitvogel, L. (2017) NKp30 Isoforms and NKp30 Ligands Are Predictive Bi-omarkers of Response to Imatinib Mesylate in Metastatic GIST Patients. OncoImmunology, 6, Article ID: e1137418. [Google Scholar] [CrossRef
[9] Ponath, V., Hoffmann, N., Bergmann, L., Mäder, C., Alashkar Alhamwe, B., Preußer, C. and Pogge Von Strandmann, E. (2021) Secreted Ligands of the NK Cell Receptor NKp30: B7-H6 Is in Contrast to BAG6 Only Marginally Released via Extracellular Vesicles. International Journal of Molecular Sciences, 22, Article No. 2189. [Google Scholar] [CrossRef] [PubMed]
[10] Pesce, S., Tabellini, G., Cantoni, C., Patrizi, O., Coltrini, D., Rampinelli, F., Matta, J., Vivier, E., Moretta, A., Parolini, S. and Marcenaro, E. (2015) B7-H6-Mediated Downregulation of NKp30 in NK cells Contributes to Ovarian Carcinoma Immune Escape. OncoImmunology, 4, Article ID: e1001224. [Google Scholar] [CrossRef
[11] Semeraro, M., Rusakiewicz, S., Minard-Colin, V., Delahaye, N.F., Enot, D., Vély, F., Marabelle, A., Papoular, B., Piperoglou, C., Ponzoni, M., Perri, P., Tchirkov, A., Matta, J., Lapierre, V., Shekarian, T., Valsesia-Wittmann, S., Commo, F., Prada, N., Poirier-Colame, V., Bressac, B., Cotteret, S., Brugieres, L., Farace, F., Chaput, N., Kroemer, G., Valteau-Couanet, D. and Zitvogel, L. (2015) Clinical Impact of the NKp30/B7-H6 Axis in High-Risk Neuroblastoma Patients. Science Translational Medicine, 7, Article No. 283ra55. [Google Scholar] [CrossRef] [PubMed]
[12] Cherif, B., Triki, H., Charfi, S., Bouzidi, L., Kridis, W.B., Khan-fir, A., Chaabane, K., Sellami-Boudawara, T. and Rebai, A. (2021) Immune Checkpoint Molecules B7-H6 and PD-L1 Co-Pattern the Tumor Inflammatory Microenvironment in Human Breast Cancer. Scientific Reports, 11, Article No. 7550. [Google Scholar] [CrossRef] [PubMed]
[13] Gutierrez-Silerio, G.Y., Franco-Topete, R.A., Haramati, J., Na-varrete-Medina, E.M., Gutierrez-Franco, J., Bueno-Topete, M.R., Bastidas-Ramirez, B.E., Ramos-Marquez, M.E. and Del Toro-Arreola, S. (2020) Positive Staining of the Immunoligand B7-H6 in Abnormal/Transformed Keratinocytes Consistently Accompanies the Progression of Cervical Cancer. BMC Immunology, 21, Article No. 9. [Google Scholar] [CrossRef] [PubMed]
[14] Jiang, T., Wu, W., Zhang, H., Zhang, X., Zhang, D., Wang, Q., Huang, L., Wang, Y. and Hang, C. (2017) High Expression of B7-H6 in Human Glioma Tissues Promotes Tumor Pro-gression. Oncotarget, 8, 37435-37447. [Google Scholar] [CrossRef] [PubMed]
[15] Zhu, Z., Teng, K.Y., Zhou, J., Xu, Y., Zhang, L., Zhao, H., Zhang, X., Tian, L., Li, Z., Lu, T., Ma, S., Li, Z., Dai, Z., Wang, J., Chen, X., Wu, X., Pan, Y., Shi, W., You, Z., Chen, H., Chung, V., Yu, J., He, S., Zhao, X., Cao, L. and Li, D. (2022) B7H6 Serves as a Negative Prognostic Marker and an Immune Modulator in Human Pancreatic Cancer. Frontiers in Oncology, 12, Article ID: 814312. [Google Scholar] [CrossRef] [PubMed]
[16] Qiu, H., Gao, S., Sun, Z. and Wang, J. (2021) Dual Role of B7-H6 as a Novel Prognostic Marker in Hepatocellular Carcinoma. APMIS, 129, 105-117. [Google Scholar] [CrossRef] [PubMed]
[17] Chen, L., Feng, J., Xu, B., Zhou, Y., Zheng, X., Wu, C. and Jiang, J. (2018) B7-H6 Expression in Human Hepatocellular Carcinoma and Its Clinical Significance. Cancer Cell International, 18, Article No. 126. [Google Scholar] [CrossRef] [PubMed]
[18] Li, D., Xiang, S., Shen, J., Xiao, M., Zhao, Y., Wu, X., Du, F., Ji, H., Li, M., Zhao, Q., Kaboli, P.J., Yang, X., Xiao, Z., Qin, B. and Wen, Q. (2020) Comprehensive Understanding of B7 Family in Gastric Cancer: Expression Profile, Association with Clinicopathological Parameters and Downstream Targets. International Journal of Biological Sciences, 16, 568-582. [Google Scholar] [CrossRef] [PubMed]
[19] Thomas, P.L., Groves, S.M., Zhang, Y.K., Li, J., Gonzalez-Ericsson, P., Sivagnanam, S., Betts, C.B., Chen, H.C., Liu, Q., Lowe, C., Chen, H., Boyd, K.L., Kopparapu, P.R., Yan, Y., Coussens, L.M., Quaranta, V., Tyson, D.R., Iams, W. and Lovly, C.M. (2021) Beyond PD-L1: B7-H6 Emerges as a Potential Immunotherapy Target in Small Cell Lung Cancer. Journal of Thoracic Oncology, 26, 1211-1223. [Google Scholar] [CrossRef] [PubMed]
[20] Zhang, X., Xie, W., Wang, Z., Song, S., Qin, Y., Zhang, F., Chen, F. and Cai, L. (2020) Expression of a Novel Immune Checkpoint B7-H6 Ligand in Human Small Cell Lung Cancer. Annals of Translational Medicine, 8, Article No. 589. [Google Scholar] [CrossRef] [PubMed]
[21] Zhao, L., Lian, T., Li, J., Wei, S., Li, H., Li, C. and Wang, H. (2021) NCR3LG1 (B7-H6) Is a Potential Prognostic Factor for Bladder Cancer Patients. Biomarkers, 26, 260-267. [Google Scholar] [CrossRef
[22] Zhang, B., Sun, J., Yao, X., Li, J., Tu, Y., Yao, F. and Sun, S. (2018) Knockdown of B7H6 Inhibits Tumor Progression in Triple-Negative Breast Cancer. Oncology Letters, 16, 91-96. [Google Scholar] [CrossRef] [PubMed]
[23] Che, F., Xie, X., Wang, L., Su, Q., Jia, F., Ye, Y., Zang, L., Wang, J., Li, H., Quan, Y., You, C., Yin, J., Wang, Z., Li, G., Du, Y. and Wang, L. (2018) B7-H6 Expression Is In-duced by Lipopolysaccharide and Facilitates Cancer Invasion and Metastasis in Human Gliomas. International Im-munopharmacology, 59, 318-327. [Google Scholar] [CrossRef] [PubMed]
[24] Yuan, L., Sun, L., Yang, S., Chen, X., Wang, J., Jing, H., Zhao, Y. and Ke, X. (2021) B7-H6 Is a New Potential Biomarker and Therapeutic Target of T-Lymphoblastic Lymphoma. An-nals of Translational Medicine, 9, Article No. 328. [Google Scholar] [CrossRef] [PubMed]
[25] Banu, N., Riera-Leal, A., Haramati, J., Ortiz-Lazareno, P.C., Panikar, S.S., Bastidas-Ramirez, B.E., Gutierrez-Silerio, G.Y., Solorzano-Ibarra, F., Tellez-Ba?Uelos, M.C., Gutierrez-Franco, J., Bueno-Topete, M.R., Pereira-Suarez, A.L. and Del Toro-Arreola, S. (2020) B7-H6, an Immunoligand for the Natural Killer Cell Activating Receptor NKp30, Reveals Inhibitory Effects on Cell Proliferation and Migration, but Not Apoptosis, in Cervical Cancer Derived-Cell lines. BMC Cancer, 20, Article No.1083. [Google Scholar] [CrossRef] [PubMed]
[26] Sheffer, M., Lowry, E., Beelen, N., Borah, M., Amara, S.N., Mader, C.C., Roth, J.A., Tsherniak, A., Freeman, S.S., Dashevsky, O., Gandolfi, S., Bender, S., Bryan, J.G., Zhu, C., Wang, L., Tariq, I., Kamath, G.M., Simoes, R.M., Dhimolea, E., Yu, C., Hu, Y., Dufva, O., Giannakis, M., Syrgkanis, V., Fraenkel, E., Golub, T., Romee, R., Mustjoki, S., Culhane, A.C., Wieten, L. and Mitsiades, C.S. (2021) Ge-nome-Scale Screens Identify Factors Regulating Tumor Cell Responses to Natural Killer Cells. Nature Genetics, 53, 1196-1206. [Google Scholar] [CrossRef] [PubMed]
[27] Chen, W., Mou, K.Y., Solomon, P., Aggarwal, R., Leung, K.K. and Wells, J.A. (2021) Large Remodeling of the Myc- Induced Cell Surface Proteome in B Cells and Pros-tate Cells Creates New Opportunities for Immunotherapy. Proceedings of the National Academy of Sciences of the United States of America, 118, Article ID: e2018861118. [Google Scholar] [CrossRef] [PubMed]
[28] Cao, G., Cheng, Y., Zheng, X., Wei, H., Tian, Z., Sun, R. and Sun, H. (2021) All-Trans Retinoic Acid Induces Leukemia Resistance to NK Cell Cytotoxicity by Down-Regulating B7-H6 Expression via c-Myc Signaling. Cancer Communications, 41, 51-61. [Google Scholar] [CrossRef] [PubMed]
[29] Obiedat, A., Charpak-Amikam, Y., Tai-Schmiedel, J., Seidel, E., Ma-hameed, M., Avril, T., Stern-Ginossar, N., Springuel, L., Bolsée, J, Gilham, D.E., Dipta, P., Shmuel, M., Chevet, E., Mandelboim, O. and Tirosh, B. (2020) The Integrated Stress Response Promotes B7H6 Expression. Journal of Molecu-lar Medicine, 98, 135-148. [Google Scholar] [CrossRef] [PubMed]
[30] Li, Y.-M., Liu, Z.-Y., Li, Z.-C., Wang, J.-C., Yu, J.-M., Yang, H.-J., Chen, Z.-N. and Tang, J. (2019) Alterations of the Immunologic Co-Stimulator B7 and TNFR Families Correlate with Hepatocellular Carcinoma Prognosis and Metastasis by Inactivating STAT3. International Journal of Molecular Sciences, 20, Article No. 156. [Google Scholar] [CrossRef] [PubMed]
[31] Baragano Raneros, A., Rodriguez, R.M., Bernardo Florez, A., Palomo, P., Colado, E., Minguela, A., Suarez Alvarez, B. and Lopez-Larrea, C. (2021) Bromodomain Protein BRD4 Is an Epige-netic Activator of B7-H6 Expression in Acute Myeloid Leukemia. OncoImmunology, 10, Article ID: 1897294. [Google Scholar] [CrossRef
[32] Chen, H., Guo, Y., Sun, J., Dong, J., Bao, Q., Zhang, X. and Fu, F. (2020) Preferential Expression of B7-H6 in Glioma Stem-Like Cells Enhances Tumor Cell Proliferation via the c-Myc/RNMT Axis. Journal of Immunology Research, 2020, Article ID: 2328675. [Google Scholar] [CrossRef] [PubMed]
[33] Yang, S., Yuan, L., Wang, Y., Zhu, M., Wang, J. and Ke, X. (2020) B7-H6 Promotes Cell Proliferation, Migration and Invasion of Non-Hodgkin Lymphoma via Ras/MEK/ERK Pathway Based on Quantitative Phosphoproteomics Data. OncoTargets and Therapy, 13, 5795-5805. [Google Scholar] [CrossRef
[34] Butler, S.E., Brog, R.A., Chang, C.H., Sentman, C.L., Huang, Y.H. and Ackerman, M.E. (2021) Engineering a Natural Ligand-Based CAR: Directed Evolution of the Stress-Receptor NKp30. Cancer Immunology, Immunotherapy, 71, 165-176. [Google Scholar] [CrossRef] [PubMed]
[35] Gacerez, A.T. and Sentman, C.L. (2018) T-Bet Promotes Potent Antitumor Activity of CD4+ CAR T Cells. Cancer Gene Therapy, 25, 117-128. [Google Scholar] [CrossRef] [PubMed]
[36] Gacerez, A.T., Hua, C.K., Ackerman, M.E. and Sentman, C.L. (2018) Chimeric Antigen Receptors with Human scFvs Preferentially Induce T Cell Anti-Tumor Activity against Tumors with High B7H6 Expression. Cancer Immunology, Immunotherapy, 67, 749-759. [Google Scholar] [CrossRef] [PubMed]
[37] Sun, X., Zhao, J., Ma, L., Sun, X., Ge, J., Yu, Y., Ma, J. and Zhang, M. (2021) B7-H6 as an Efficient Target for T Cell-Induced Cytotoxicity in Haematologic Malignant Cells. Inves-tigational New Drugs, 39, 24-33. [Google Scholar] [CrossRef] [PubMed]