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Murine B7-H3 Is a Negative Regulator of T Cells
Open accessAbstract
T cell activation is regulated by the innate immune system through positive and negative costimulatory molecules. B7-H3 is a novel B7-like molecule with a putative receptor on activated T cells. Human B7-H3 was first described as a positive costimulator, most potently inducing IFN-gamma production and cellular immunity. In this study we examined the expression and function of mouse B7-H3. B7-H3 is mostly expressed on professional APCs; its expression on dendritic cells appears to be up-regulated by LPS. In contrast to human B7-H3, we found that mouse B7-H3 protein inhibited T cell activation and effector cytokine production. An antagonistic mAb to B7-H3 enhanced T cell proliferation in vitro and led to exacerbated experimental autoimmune encephalomyelitis in vivo. Therefore, mouse B7-H3 serves as a negative regulator of T cell activation and function.
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“Interestingly, CD276 (B7-H3), known to augment Tregs and inhibit T cell responses (Costa et al., 2018, Prasad et al., 2004, Suh et al., 2003), was expressed most prominently on CAFs and TSKs.”
From Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020) · cites this paper as Prasad et al., 2004
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“Interestingly, CD276 (B7-H3), known to augment Tregs and inhibit T cell responses (Costa et al., 2018; Prasad et al., 2004; Suh et al., 2003), was expressed most prominently on CAFs and TSKs.”
BackgroundNovel immune checkpoint targets: moving beyond PD-1 and CTLA-4
Qin, S., Xu, L., Yi, M., Yu, S., Wu, K., & Luo, S. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1091-2 · Cited by 1,145
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“B7-H3 is constitutively expressed on murine APCs (Collins et al., 2005), but inducibly expressed on human T cells, NK cells, DCs, macrophages, and monocytes (Chapoval et al., 2001; Prasad et al., 2004; Steinberger et al., 2004; Suh et al., 2003).”
Senescence-Associated Exosome Release from Human Prostate Cancer Cells
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B7-H3: An Attractive Target for Antibody-based Immunotherapy
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“Indeed, B7-H3 expression on antigen-presenting cells (APC) reduces CD4þ and CD8þ T-cell activation, as well as effector cytokine release (28).”
BackgroundCancer prevention and therapy through the modulation of the tumor microenvironment
Casey, S. C., Amedei, A., Aquilano, K., Azmi, A. S., Benencia, F., Bhakta-Guha, D., Bilsland, A. E., Boosani, C. S., Chen, S., Ciriolo, M. R., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.02.007 · Cited by 379
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Self-citationThe B7 family of immune-regulatory ligands.
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Emerging targets in cancer immunotherapy
Burugu, S., Dancsok, A. R., & Nielsen, T. O. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.10.001 · Cited by 320
B7-H3 and B7-H4 expression in non-small-cell lung cancer
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CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance
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Co-stimulatory and Co-inhibitory Pathways in Autoimmunity
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“B7-H3 blockade resulted in enhanced EAE, whereas mice deficient in B7-H3 showed reduced disease severity and production of Th1 and Th17 cell cytokines (Luo et al., 2015; Prasad et al., 2004), suggesting that more analysis of this pathway is required.”
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Zhou, W.-T., & Jin, W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.701006 · Cited by 303
B7‐H3 is a potent inhibitor of human T‐cell activation: No evidence for B7‐H3 and TREML2 interaction
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Crispen, P. L., Sheinin, Y. M., Roth, T. J., Lohse, C. M., Kuntz, S. M., Frigola, X., Thompson, R. H., Boorjian, S. A., Dong, H., Leibovich, B. C., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0536 · Cited by 272
“In a separate study, plate-immobilized murine B7-H3 in the presence of anti-CD3 was shown to inhibit murine CD4 T-cell activation and interleukin-2 production, an effect that was completely abrogated by antibody-mediated B7-H3 blockade (20).”
BackgroundRoth, T. J., Sheinin, Y., Lohse, C. M., Kuntz, S. M., Frigola, X., Inman, B. A., Krambeck, A. E., Mckenney, M. E., Karnes, R. J., Blute, M. L., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1068 · Cited by 267
“In vivo antibody-mediated blockade of B7-H3 in mice has been reported to lead to elevations in T-cell activation and more severe forms of experimental autoimmune encephalitis (10, 11).”
BackgroundTumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas
Zang, X., Sullivan, P. S., Soslow, R. A., Waitz, R., Reuter, V. E., Wilton, A. S., Thaler, H. T., Arul, M., Slovin, S. F., Wei, J., et al. (2010) · Modern Pathology · doi:10.1038/modpathol.2010.95 · Cited by 250
T‐cell tolerance or function is determined by combinatorial costimulatory signals
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“Negative costimulatory molecules PD-1, B7-H3 and B7S1 have been shown to regulate T-cell activation thresholds, and loss of their action often resulted in greater susceptibility to autoimmune diseases (Sharpe and Freeman, 2002; Prasad et al, 2003, 2004; Suh et al, 2003).”
BackgroundInfluentialNew B7 Family Checkpoints in Human Cancers
Ni, L., & Dong, C. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0761 · Cited by 245
VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy
Lines, J. L., Sempere, L. F., Broughton, T., Wang, L., & Noelle, R. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0072 · Cited by 236
“Both in mice and humans, there are reports that show B7-H3 acts as either a costimulatory molecule (29, 31) or a NCR (30, 32, 33).”
Cell intrinsic mechanisms of T‐cell inhibition and application to cancer therapy
Peggs, K. S., Quezada, S. A., & Allison, J. P. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00649.x · Cited by 232
“Initial studies in mice showed that antibodymediated blockade of B7-H3 resulted in enhanced T-cell proliferation in vitro as well as exacerbation of experimental autoimmune encephalomyelitis in vivo (188).”
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“In B7-H3-deficient mice Th1-mediated hypersensitivity and onset of experimental autoimmune encephalomyelitis (EAE) are promoted, and treatment with a blocking anti-B7-H3 mAb exacerbates EAE (6, 7).”
BackgroundInfluentialThe third group of the B7‐ CD 28 immune checkpoint family: HHLA 2, TMIGD 2, B7x, and B7‐H3
Janakiram, M., Shah, U. A., Liu, W., Zhao, A., Schoenberg, M., & Zang, X. (2017) · Immunological Reviews · doi:10.1111/imr.12521 · Cited by 227
CAR T cells for brain tumors: Lessons learned and road ahead
Akhavan, D., Alizadeh, D., Wang, D., Weist, M. R., Shepphird, J. K., & Brown, C. E. (2019) · Immunological Reviews · doi:10.1111/imr.12773 · Cited by 217
Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy
Zhao, B., Li, H., Xia, Y., Wang, Y., Wang, Y., Shi, Y., Xing, H., Qu, T., Wang, Y., & Ma, W. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01364-7 · Cited by 213
“blocking B7-H3 enhanced T cell activation in murine models [97].”
BackgroundHofmeyer, K. A., Ray, A., & Zang, X. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805458105 · Cited by 203
“Anti-B7-H3 antibodies augmented the severity of experimental autoimmune encephalomyelitis (EAE) and allergic conjunctivitis (18, 19), suggesting B7-H3 inhibits Th1, Th2, or Th17 in vivo.”
BackgroundBTNL2, a Butyrophilin-Like Molecule That Functions to Inhibit T Cell Activation
Nguyen, T. D., Liu, X. K., Zhang, Y., & Dong, C. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.12.7354 · Cited by 194
“Human B7-H3 was first found to be a positive costimulator (15); recent studies by others suggested that mouse B7-H3 may serve as a negative regulator in T cell activation (16, 17).”
BackgroundZhang, G., Hou, J., Shi, J., Yu, G., Lu, B., & Zhang, X. (2008) · Immunology · doi:10.1111/j.1365-2567.2007.02723.x · Cited by 193
The New B7s: Playing a Pivotal Role in Tumor Immunity
Flies, D. B., & Chen, L. (2007) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31802e085a · Cited by 192
Chen, X., Song, X., Li, K., & Zhang, T. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00292 · Cited by 179
Fine tuning the immune response through B7‐H3 and B7‐H4
Yi, K. H., & Chen, L. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00768.x · Cited by 172
“Recombinant mouse and human B7-H3 proteins were shown to inhibit anti-CD3 mAb-induced T-cell proliferation, cytokine production, and activation of transcription factors, such as nuclear factor for activated T cells (NFAT), nuclear factor jB (NF-jB), and activator protein-1 (AP-1) (3, 19, 20).”
BackgroundB7-H3 role in the immune landscape of cancer.
Castellanos, J. R., Purvis, I. J., Labak, C. M., Guda, M. R., Tsung, A. J., Velpula, K. K., & Asuthkar, S. (2017) · Europe PMC (PubMed Central) · Cited by 172
Clinical importance of B7-H3 expression in human pancreatic cancer
Yamato, I., Sho, M., Nomi, T., Akahori, T., Shimada, K., Hotta, K., Kanehiro, H., Konishi, N., Yagita∥, H., & Nakajima, Y. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605375 · Cited by 169
“In vivo antibodymediated blockade of B7-H3 in mice has been reported to enhance T-cell activation and to lead to more severe forms of experimental autoimmune encephalitis (Suh et al, 2003; Prasad et al, 2004).”
BackgroundB7-H3 Negatively Modulates CTL-Mediated Cancer Immunity
Yonesaka, K., Haratani, K., Takamura, S., Sakai, H., Kato, R., Takegawa, N., Takahama, T., Tanaka, K., Hayashi, H., Takeda, M., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2852 · Cited by 169
“Although B7-H3 was initially identified as an activator of T-cell function (32, 33), subsequent reports have shown that B7-H3 can cause T-cell dysfunction (37, 38).”
ResultRegulation of T cell activation and tolerance by PDL2
Zhang, Y., Chung, Y., Bishop, C., Daugherty, B., Chute, H. T., Holst, P. L., Kurahara, C., Lott, F. D., Sun, N., Welcher, A. A., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601347103 · Cited by 163
Sun, J., Chen, L., Zhang, G., Jiang, J., Zhu, M. L., Tan, Y. Q., Wang, H.-T., Lu, B., & Zhang, X. (2010) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-010-0841-1 · Cited by 159
“B7-H3 has been implied to play an immune suppressive role in cancer mainly based on evidence obtained by studying its function in autoimmune diseases [ 28 , 37].”
BackgroundScribner, J. A., Brown, J. G., Son, T., Chiechi, M., Li, P., Sharma, S., Li, H., Costa, A. D., Li, Y., Chen, Y., et al. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0116 · Cited by 155
Yin–Yang of costimulation: crucial controls of immune tolerance and function
Nurieva, R. I., Liu, X., & Dong, C. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00769.x · Cited by 157
“Similarly to B7-H3 and B7S1 (91, 99), we found plate-bound BTNL2–Ig moderately reduced IL-2 production when CD4 T cells were activated with anti-CD3 alone or together with anti-CD28.”
BackgroundMethodInfluentialSelf-citationKang, F., Ling, W., Jia, H.-C., Li, D., Li, H., Zhang, Y., & Sun, D. (2015) · Cancer Cell International · doi:10.1186/s12935-015-0195-z · Cited by 156
“Others evidence showed that B7-H3 played an inhibitory role during autoimmune diseases [11,12].”
BackgroundMiyamoto, T., Murakami, R., Hamanishi, J., Tanigaki, K., Hosoe, Y., Mise, N., Takamatsu, S., Mise, Y., Ukita, M., Taki, M., et al. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0407 · Cited by 156
“Not only does it exert its immunomodulatory effects by directly acting on target cells as an immune checkpoint (15, 19, 20), it is also involved in the intracellular signaling of cancer cells, such as the STAT3 pathway (21–23).”
Aggarwal, C., Prawira, A., Antonia, S. J., Rahma, O. E., Tolcher, A. W., Cohen, R. B., Lou, Y., Hauke, R. J., Vogelzang, N. J., Zandberg, D. P., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004424 · Cited by 153
Loos, M., Hedderich, D. M., Ottenhausen, M., Giese, N. A., Laschinger, M., Esposito, I., Kleeff, J. H., & Friess, H. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-463 · Cited by 150
“Although these results clearly implicate a tumor-protective effect of B7-H3, the exact physiologic/pathologic role of B7-H3 remains ambiguous, because B7-H3 has also been shown to inhibit CD4+ and CD8+ T cell proliferation and IFN-γ production mediated by anti-CD3 in mice [28].”
ResultNot All Immune Checkpoints Are Created Equal
Linhares, A. D. S., Leitner, J. M., Grabmeier‐Pfistershammer, K., & Steinberger, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01909 · Cited by 157
B7–H3 Ligand Expression by Primary Breast Cancer and Associated With Regional Nodal Metastasis
Arigami, T., Narita, N., Mizuno, R., Nguyen, L., Ye, X., Chung, A. P., Giuliano, A. E., & Hoon, D. S. �. (2010) · Annals of Surgery · doi:10.1097/sla.0b013e3181f1939d · Cited by 144
“0001 >2 cm and ≤5 cm (T2) 14 (28) 8 (25) >5 cm (T3) 9 (18) 23 (72) AJCC stage I 18 (36) 1 (3) <0.”
New checkpoints in cancer immunotherapy
Ni, L., & Dong, C. (2017) · Immunological Reviews · doi:10.1111/imr.12524 · Cited by 143
Novel targets for immune-checkpoint inhibition in cancer
Borgeaud, M., Sandoval, J. L., Obéid, M., Banna, G. L., Michielin, O. A., Addeo, A., & Friedlaender, A. (2023) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2023.102614 · Cited by 150
Arnett, H. A., Escobar, S. M., González‐Suárez, E., Budelsky, A., Steffen, L. A., Boiani, N., Zhang, M., Siu, G., Brewer, A. W., & Viney, J. L. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.3.1523 · Cited by 139
“B7-H3, another B7 homolog (16, 17), binds an unidentified receptor on activated T cells and serves as a negative regulator of T cell activation (18).”
BackgroundStructure and T Cell Inhibition Properties of B7 Family Member, B7-H3
Vigdorovich, V. I., Ramagopal, U. A., Lázár‐Molnár, E., Sylvestre, E., Lee, J. S., Hofmeyer, K. A., Zang, X., Nathenson, S. G., & Almo, S. C. (2013) · Structure · doi:10.1016/j.str.2013.03.003 · Cited by 136
“B7-H3 function has been previously evaluated in T cell proliferation assays (Chapoval et al., 2001; Suh et al., 2003; Prasad et al., 2004).”
InfluentialEstriol Generates Tolerogenic Dendritic Cells In Vivo That Protect against Autoimmunity
Papenfuss, T. L., Powell, N. D., McClain, M. A., Bedarf, A., Singh, A. J., Gienapp, I. E., Shawler, T. M., & Whitacre, C. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001322 · Cited by 144
Mahnke, K., Ring, S., Johnson, T., Schallenberg, S., Schönfeld, K., Storn, V., Bedke, T., & Enk, A. (2007) · European Journal of Immunology · doi:10.1002/eji.200636841 · Cited by 136
B7-H3-Targeted CAR-T Cells Exhibit Potent Antitumor Effects on Hematologic and Solid Tumors
Zhang, Z., Jiang, C., Liu, Z., Yang, M., Tang, X., Wang, Y., Zheng, M., Huang, J., Zhong, K., Zhao, S., et al. (2020) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2020.03.019 · Cited by 134
“B7-H3 (CD276) is a type I transmembrane protein that belongs to the B7 family.(6) Although B7-H3 was originally reported as a positive costimulator of T cells in humans,(7) increasing evidence suggests that it may be a negative regulator.”
BackgroundCai, D., Li, J., Liu, D., Hong, S., Qiao, Q., Sun, Q., Li, P., Lyu, N., Sun, T., Xie, S., et al. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0305-2 · Cited by 136
Recent developments in immunotherapy for gastrointestinal tract cancers
Chong, X., Madeti, Y., Cai, J., Li, W., Cong, L., Lu, J., Mo, L., Liu, H., He, S., Yu, C., et al. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01578-x · Cited by 132
B7‐H3 and Its Role in Antitumor Immunity
Loos, M., Hedderich, D. M., Friess, H., & Kleeff, J. H. (2010) · Journal of Immunology Research · doi:10.1155/2010/683875 · Cited by 117
“Furthermore, an antagonistic mAb to B7-H3 enhanced T-cell proliferation in vitro and led to exacerbated experimental autoimmune encephalomyelitis (EAE) in vivo [39].”
BackgroundLuo, L., Zhu, G., Xu, H., Yao, S., Zhou, G., Zhu, Y., Tamada, K., Huang, L., Flies, A. S., Broadwater, M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130126 · Cited by 115
“For example, infusion of a B7-H3 mAb accelerated the progression of diseases with an enhanced Th1 T cell response in a MOG peptide-induced EAE model [19].”
BackgroundClinical Insights Into Novel Immune Checkpoint Inhibitors
Lee, J. B., Ha, S., & Kim, H. R. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.681320 · Cited by 115
“Recently, the co-inhibitory function of B7-H3 in CD4 and CD8 T cells was discovered (Suh et al., 2003; Prasad et al., 2004).”
BackgroundMiyamoto, T., Murakami, R., Hamanishi, J., Tanigaki, K., Hosoe, Y., Mise, N., Takamatsu, S., Mise, Y., Ukita, M., Taki, M., et al. (2022) · Institutional Repositories DataBase (IRDB) · doi:10.14989/doctor.k23801 · Cited by 112
The nature of activatory and tolerogenic dendritic cell-derived signal II
Bakdash, G., Sittig, S. P., van Dijk, T., Figdor, C. G., & de Vries, I. J. M. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00053 · Cited by 126
Histone lactylation-driven B7-H3 expression promotes tumor immune evasion
Ma, Z., Yang, J., Jia, W., Li, L., Li, Y., Hu, J., Luo, W., Li, R., Ye, D., & Lan, P. (2025) · Theranostics · doi:10.7150/thno.105947 · Cited by 113
Chen, C., Shen, Y., Qu, Q., Chen, X., Zhang, X., & Huang, J. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.09.006 · Cited by 105
B7-H3 as a Therapeutic Target in Advanced Prostate Cancer
Guo, C. W., Figueiredo, I., Gürel, B., Neeb, A., Seed, G., Crespo, M., Carreira, S., Rekowski, J., Buroni, L., Welti, J. C., et al. (2022) · European Urology · doi:10.1016/j.eururo.2022.09.004 · Cited by 113
B7-H3 overexpression in pancreatic cancer promotes tumor progression
ZHAO, X., Li, D., Zhu, X., Gan, W.-J., Li, Z., XIONG, F., Zhang, Z., Zhang, G., Zhang, X., & Zhao, H. (2012) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2012.1212 · Cited by 104
“Previous studies found that B7-H3 deficient mice show airway inflammation (16), experimental autoimmune encephalitis (17) and allergic conjunctivitis in an accelerated pattern (18).”
B7‐H3 promotes acute and chronic allograft rejection
Wang, L., Fraser, C. C., Kikly, K. K., Wells, A. D., Han, R., Coyle, A. J., Chen, L., & Hancock, W. W. (2005) · European Journal of Immunology · doi:10.1002/eji.200425518 · Cited by 102
Immunoexpression of B7-H3 in endometrial cancer: Relation to tumor T-cell infiltration and prognosis
Brunner, A. H., Hinterholzer, S., RISS, P. A., Heinze, G., & Brustmann, H. (2011) · Gynecologic Oncology · doi:10.1016/j.ygyno.2011.09.012 · Cited by 100
Schneider, T., Hoffmann, H., Dienemann, H., Schnabel, P. A., Enk, A., Ring, S., & Mahnke, K. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31821c421d · Cited by 98
Li, Y., Huang, J., Foley, N. M., Xu, Y., Li, Y. P., Pan, J., Redmond, H. P., Wang, J. H., & Wang, J. (2016) · Scientific Reports · doi:10.1038/srep31284 · Cited by 98
Bolandi, N., Derakhshani, A., Hemmat, N., Baghbanzadeh, A., Asadzadeh, Z., Nour, M. A., Brunetti, O., Bernardini, R., Silvestris, N., & Baradaran, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910719 · Cited by 97
“In comparison to the co-stimulatory role of B7-H3, most studies have generally shown that B7-H3 predominantly has a negative regulating role on T lymphocytes in humans and murine [90,91].”
ResultCostimulation, Coinhibition and Cancer
Inman, B. A., Frigola, X., Dong, H., & Kwon, E. D. (2007) · Current Cancer Drug Targets · doi:10.2174/156800907780006878 · Cited by 97
“Studies evaluating the precise physiologic role of B7-H3 are conflicting: some groups found evidence suggesting that B7-H3 has positive costimulatory properties [70], other groups have found the exact opposite [71,72].”
BackgroundB7-H3 Augments the Inflammatory Response and Is Associated with Human Sepsis
Zhang, G., Wang, J., Kelly, J., Gu, G., Hou, J., Zhou, Y., Redmond, H. P., Wang, J. H., & Zhang, X. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904020 · Cited by 94
“In contrast, other groups have reported a negative regulatory function for both human and mouse B7-H3 in T cellmediated immune responses, including an inhibitory effect of B7-H3 on anti-CD3 mAb-induced both T cell proliferation and cytokine production (11, 12, 17).”
BackgroundThe CD28-B7 Family in Anti-Tumor Immunity: Emerging Concepts in Cancer Immunotherapy
Leung, J., & Suh, W. (2014) · Immune Network · doi:10.4110/in.2014.14.6.265 · Cited by 92
B7-H3 Over Expression in Prostate Cancer Promotes Tumor Cell Progression
Yuan, H., Wei, X., Zhang, G., Li, C., Zhang, X., & Hou, J. (2011) · The Journal of Urology · doi:10.1016/j.juro.2011.04.103 · Cited by 89
Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment
Ziogas, D. C., Theocharopoulos, C., Lialios, P., Foteinou, D., Koumprentziotis, I., Xynos, G., & Gogas, H. J. (2023) · Cancers · doi:10.3390/cancers15102718 · Cited by 95
“who described that B7-H3 downregulates NFAT, NF-kB and AP-1 transcriptional factors and consequently restricts T-cell function and effector cytokine secretion [236].”
BackgroundMolecular mechanisms of T‐cell tolerance
Nurieva, R., Liu, X., & Dong, C. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01012.x · Cited by 92
“Two groups found that mouse B7-H3 protein inhibited T-cell activation and effector cytokine production in both CD4 and CD8 T cells (48, 49).”
BackgroundDiagnosis value of serum B7-H3 expression in non-small cell lung cancer
Zhang, G., Xu, Y., Lü, X., Huang, H., Zhou, Y., Lu, B., & Zhang, X. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.01.017 · Cited by 89
Petroff, M. G., Kharatyan, E., Torry, D. S., & Holets, L. M. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62990-2 · Cited by 86
The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy
Russell, B. L., Sooklal, S. A., Malindisa, S. T., Daka, L. J., & Ntwasa, M. M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.641428 · Cited by 86
Expression of Immunosuppresive B7-H3 Ligand by Hormone-Treated Prostate Cancer Tumors and Metastases
Chavin, G., Sheinin, Y. M., Crispen, P. L., Boorjian, S. A., Roth, T. J., Rangel, L. J., Blute, M. L., Sebo, T. J., Tindall, D., Kwon, E. D., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2262 · Cited by 82
Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity
Archilla‐Ortega, A., Domuro, C., Martín-Liberal, J., & Muñoz, P. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02264-x · Cited by 79
“Conversely, B7-H3 signaling in T cells is also able to inhibit them by blocking TCR signaling [102].”
BackgroundLi, H., Yang, Z., & Guo, Q. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00789-w · Cited by 86
“However, later studies showed that B7-H3, as a member of the B7 family, acts more as a negative regulator to inhibit the immune response of T cells [94, 95].”
BackgroundVeenstra, R. G., Flynn, R. P., Kreymborg, K. G., McDonald-Hyman, C. S., Saha, A., Taylor, P. A., Osborn, M. J., Panoskaltsis‐Mortari, A., Schmitt-Graeff, A. H., Lieberknecht, E., et al. (2015) · Blood · doi:10.1182/blood-2014-09-603357 · Cited by 77
“We observed more IFN-g production in recipients of B7-H3 donor T cells, consistent with other studies, which showed that inhibiting B7-H3 led to increased IFN-g secretion as well as increased proliferation.(2,11,12) Increased gut epithelial damage could result from increased T effector proliferation, inflammatory cyto…”
BackgroundResultGeneration and Characterization of B7-H4/B7S1/B7x-Deficient Mice
Suh, W., Wang, S., Duncan, G. S., Miyazaki, Y., Cates, E. C., Walker, T. D., Gajewska, B., Deenick, E. K., Dawicki, W., Okada, H., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00755-06 · Cited by 78
“We and others have shown that B7-H3 and its unknown receptor(s) downregulate T-cell responses both in vitro and in vivo (16, 23, 34).”
BackgroundShi, W. M., Wang, Y., Zhao, Y., Kim, J. J., Li, H., Meng, C., Chen, F., Zhang, J., Mak, D. H. F., Van, V., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adf6724 · Cited by 80
“Luminal cells (22,495) were subset from the whole dataset to identify aneuploid cells and investigate gene expression of CD276, PTEN, and TP53.”
BackgroundXiong, G., Chen, Z., Liu, Q., Peng, F., Zhang, C., Cheng, M., Ling, R., Chen, S., Liang, Y., Chen, D., et al. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008662 · Cited by 74
Vasaturo, A., Blasio, S. D., Peeters, D. G. A., de Koning, C. C. H., de Vries, I. J. M., Figdor, C. G., & Hato, S. V. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00417 · Cited by 76
“However, it has also been reported that antagonistic antibodies could enhance in vitro T cell proliferation (111).”
BackgroundEmerging Immunotherapy for Acute Myeloid Leukemia
Tabata, R., Chi, S., Yuda, J., & Minami, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041944 · Cited by 74
“B7-homolog 3 (B7-H3; also known as CD276) is one of the B7 family molecules normally expressed on activated APCs and negatively regulates T-cell activation [67].”
BackgroundRegulation of costimulation in the era of butyrophilins
Arnett, H. A., Escobar, S. M., & Viney, J. L. (2009) · Cytokine · doi:10.1016/j.cyto.2009.03.009 · Cited by 71
An Orthotopic Colon Cancer Model for Studying the B7-H3 Antitumor Effect In Vivo
Lupu, C., Eisenbach, C., Kuefner, M. A., Schmidt, J., Lupu, A., Stremmel, W., & Encke, J. (2006) · Journal of Gastrointestinal Surgery · doi:10.1007/bf03239969 · Cited by 68
REVIEW ARTICLE: B7 Family Molecules as Regulators of the Maternal Immune System in Pregnancy
Petroff, M. G., & Perchellet, A. (2010) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2010.00841.x · Cited by 67
Tran, C. N., Thacker, S. G., Louie, D. M., Oliver, J. A., White, P. T., Endres, J., Urquhart, A. G., Chung, K. C., & Fox, D. A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.2989 · Cited by 66
“shown that B7-H3 can mediate inhibitory effects (17, 19, 20) on T cell”
BackgroundRing, S., Maas, M., Nettelbeck, D. M., Enk, A., & Mahnke, K. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202592 · Cited by 66
Yim, J., Koh, J., Kim, S., Song, S. G., Ahn, H. K., Kim, Y. A., Jeon, Y. K., & Chung, D. H. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.03.033 · Cited by 67
Peuker, K., Strigli, A., Tauriello, D. V. F., Hendricks, A., Schönfels, W. V., Burmeister, G., Brosch, M., Herrmann, A., Krüger, S., Nitsche, J., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.03.008 · Cited by 68
The Role of Coinhibitory Signaling Pathways in Transplantation and Tolerance
McGrath, M. M., & Najafian, N. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00047 · Cited by 63
“B7-H3 IN DISEASE STATES In vivo, treatment with an antagonistic mAb, anti-B7-H3, lead to earlier onset of EAE, more clinically severe disease and greater numbers of brain-infiltrating CD4+ T cells in treated than controls (Prasad et al., 2004).”
BackgroundMethodResultInfluentialB7-H3 expression in ductal and lobular breast cancer and its association with IL-10
Liu, C., Liu, J., Wang, J., Liu, Y., Zhang, F., LIN, W., Gao, A., Sun, M., Wang, Y., & Sun, Y. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.1158 · Cited by 63
Ma, L., Luo, L., Qiao, H., Dong, X., Pan, S., Jiang, H., Krissansen, G. W., & Sun, X. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.07.031 · Cited by 61
“B7H3 is a controversial anti-cancer agent, as two previous reports indicated that B7-H3 negatively regulates T cell responses in mice by inhibiting T cell proliferation, IL-2 production, and Th1-mediated responses which are essential to generate effective anti-tumor immunity [33,34].”
Background
Metadata
- Authors
- Prasad, D. V. R., Nguyen, T., Li, Z., Yang, Y., Duong, J., Wang, Y., & Dong, C.
- Affiliations
- University of Washington (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-08
- Volume
- 173
- Issue
- 4
- Pages
- 2500-2506
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2110172571
- Cited by
- 368
- References
- 42
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 30 · 2023: 22 · 2022: 27 · 2021: 34 · 2020: 27 · 2019: 18 · 2018: 10 · 2017: 16 · 2016: 11 · 2015: 11 · 2014: 6 · 2013: 14 · 2012: 17
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- B7-H3, T cell activation, dendritic cells, professional antigen-presenting cells, IFN-gamma production, experimental autoimmune encephalomyelitis, T cell proliferation, mice
- MeSH terms
- Animals, Antigen-Presenting Cells, B-Lymphocytes, Cells, Cultured, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, Female, Flow Cytometry, Lymphocyte Activation, Macrophages, T-Lymphocytes, Cytokines, B7-1 Antigen, Antibodies, Blocking, Mice, Rats, B7 Antigens
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