Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Abstract
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in the regulation of cellular and humoral immune responses through the PD-1 receptor on activated T and B cells. We report here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1. In contrast, B7-H1 is abundant in human carcinomas of lung, ovary and colon and in melanomas. The pro-inflammatory cytokine interferon-gamma upregulates B7-H1 on the surface of tumor cell lines. Cancer cell-associated B7-H1 increases apoptosis of antigen-specific human T-cell clones in vitro, and the apoptotic effect of B7-H1 is mediated largely by one or more receptors other than PD-1. In addition, expression of B7-H1 on mouse P815 tumor increases apoptosis of activated tumor-reactive T cells and promotes the growth of highly immunogenic B7-1(+) tumors in vivo. These findings have implications for the design of T cell-based cancer immunotherapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Expression of inhibitory immune checkpoint molecules is often mis-regulated in human cancers in order to escape immune surveillance.
“their expression is often mis-regulated in human cancers in order to escape immune surveillance [3,4].”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [3]
Cites
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294 · see citing works
Nagata, S., & Golstein, P. (1995) · Science · doi:10.1126/science.7533326 · Cited by 3,979 · see citing works
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259 · see citing works
Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80089-8 · Cited by 2,749 · see citing works
CD28/B7 SYSTEM OF T CELL COSTIMULATION
Lenschow, D. J., Walunas, T. L., & Bluestone, J. A. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.233 · Cited by 2,717 · see citing works
Dong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496 · see citing works
Self-citationFas Ligand-Induced Apoptosis as a Mechanism of Immune Privilege
Griffith, T. S., Brunner, T., Fletcher, S. M., Green, D. R., & Ferguson, T. A. (1995) · Science · doi:10.1126/science.270.5239.1189 · Cited by 1,990 · see citing works
Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice
Nishimura, H., Okazaki, T., Tanaka, Y., Nakatani, K., Hara, M., Matsumori, A., Sasayama, S., Mizoguchi, A., Hiai, H., Minato, N., et al. (2001) · Science · doi:10.1126/science.291.5502.319 · Cited by 1,868 · see citing works
Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes
Agata, Y., Kawasaki, A., Nishimura, H., Ishida, Y., Tsubat, T., Yagita, H., & Honjo, T. (1996) · International Immunology · doi:10.1093/intimm/8.5.765 · Cited by 1,589 · see citing works
Linsley, P. S., Greene, J. L., Brady, W., Bajorath, J., Ledbetter, J. A., & Peach, R. (1994) · Immunity · doi:10.1016/s1074-7613(94)80021-9 · Cited by 977 · see citing works
Krummel, M. F., & Allison, J. P. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2533 · Cited by 923 · see citing works
CTLA-4 ligation blocks CD28-dependent T cell activation.
Walunas, T. L., Bakker, C. Y., & Bluestone, J. A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2541 · Cited by 801 · see citing works
A fresh look at tumor immunosurveillance and immunotherapy
Smyth, M. J., Godfrey, D. I., & Trapani, J. A. (2001) · Nature Immunology · doi:10.1038/86297 · Cited by 747 · see citing works
OX40 Promotes Bcl-xL and Bcl-2 Expression and Is Essential for Long-Term Survival of CD4 T Cells
Rogers, P., Song, J. J., Gramaglia, I., Killeen, N. P., & Croft, M. (2001) · Immunity · doi:10.1016/s1074-7613(01)00191-1 · Cited by 645 · see citing works
Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity.
Chen, L., McGowan, P., Ashe, S. A., Johnston, J. A., Li, Y., Hellström, I., & Hellström, K. E. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.2.523 · Cited by 462 · see citing works
Self-citationCo-stimulation in T cell responses
Chambers, C. A., & Allison, J. P. (1997) · Current Opinion in Immunology · doi:10.1016/s0952-7915(97)80087-8 · Cited by 415 · see citing works
Cutting Edge: 4-1BB Is a Bona Fide CD8 T Cell Survival Signal
Takahashi, C., Mittler, R. S., & Vella, A. T. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.9.5037 · Cited by 385 · see citing works
T cell co-stimulatory molecules other than CD28
Watts, T. H., & DeBenedettet, M. A. (1999) · Current Opinion in Immunology · doi:10.1016/s0952-7915(99)80046-6 · Cited by 343 · see citing works
Costimulation of T cells for tumor immunity
Chen, L., Linsley, P. S., & Hellström, K. E. (1993) · Immunology Today · doi:10.1016/0167-5699(93)90262-j · Cited by 315 · see citing works
Self-citationTRAIL/Apo-2-ligand-induced apoptosis in human T cells
Jeremias, I., Herr, I., Böhler, T., & Debatin, K. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199801)28:01 · Cited by 265 · see citing works
Hurtado, J., Kim, Y. J., & Kwon, B. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.6.2600 · Cited by 260 · see citing works
CD28 costimulation prevents cell death during primary T cell activation
Noel, P. J., Boise, L., Green, J. M., & Thompson, C. B. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.2.636 · Cited by 260 · see citing works
Gene transfer of Fas ligand induces tumor regression in vivo
Arai, H., Gordon, D., Nabel, E. G., & Nabel, G. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13862 · Cited by 247 · see citing works
Nakashima, M., Sonoda, K., & Watanabe, T. (1999) · Nature Medicine · doi:10.1038/11383 · Cited by 244 · see citing works
B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function
Tamura, H., Dong, H., Zhu, G., Sica, G., Flies, D. B., Tamada, K., & Chen, L. (2001) · Blood · doi:10.1182/blood.v97.6.1809 · Cited by 218 · see citing works
Self-citationSykulev, Y. K., Brunmark, A. B., Tsomides, T. J., Kageyama, S., Jackson, M. R., Peterson, P. A., & Eisen, H. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.24.11487 · Cited by 190 · see citing works
Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas ligand.
Georgescu, L., Vakkalanka, R., Elkon, K. B., & Crow, M. K. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119806 · Cited by 174 · see citing works
Rivoltini, L., Barracchini, K. C., Viggiano, V., Kawakami, Y., Smith, A., Mixon, A., Restifo, N. P., Topalian, S. L., Simonis, T. B., & Rosenberg, S. A. (1995) · PubMed · Cited by 160 · see citing works
Boise, L., Noel, P. J., & Thompson, C. B. (1995) · Current Opinion in Immunology · doi:10.1016/0952-7915(95)80067-0 · Cited by 139 · see citing works
Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen.
Kobayashi, H., Wood, M., Song, Y., Appella, E., & Celis, E. (2000) · PubMed · Cited by 138 · see citing works
Self-citationHuman melanoma cells do not express Fas (Apo-1/CD95) ligand.
Chappell, D. B., Zaks, T. Z., Rosenberg, S. A., & Restifo, N. P. (1999) · PubMed · Cited by 133 · see citing works
Finger, L. R., Pu, J. J., Wasserman, R., Vibhakar, R., Louie, E., Hardy, R. R., Burrows, P. D., & Billips, L. G. (1997) · Gene · doi:10.1016/s0378-1119(97)00260-6 · Cited by 113 · see citing works
Tamada, K., Tamura, H., Flies, D. B., Fu, Y., Celis, E., Pease, L. R., Blazar, B. R., & Chen, L. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0213604 · Cited by 91 · see citing works
Self-citationImmune evasion by tumours: involvement of the CD95 (APO-1/Fas) system and its clinical implications
Strand, S., & Galle, P. R. (1998) · Molecular Medicine Today · doi:10.1016/s1357-4310(97)01191-x · Cited by 78 · see citing works
Fas counter-attack–the best form of tumor defense?
O’Connell, J., Bennett, M. W., O'Sullivan, G., Collins, J. K., & Shanahan, F. (1999) · Nature Medicine · doi:10.1038/6477 · Cited by 71 · see citing works
Lu, J., & Celis, E. (2000) · PubMed · Cited by 67 · see citing works
Self-citationFunctional expression of TRAIL by lymphoid and myeloid tumour cells
Zhao, S., Asgari, Z., Wang, Y., Goodwin, R. G., Andreeff, M., & Younes, A. (1999) · British Journal of Haematology · doi:10.1046/j.1365-2141.1999.01630.x · Cited by 41 · see citing works
Immunoglobulin Fusion Proteins as a Tool for Evaluation of T-Cell Costimulatory Molecules
Chapoval, A. I., Zhu, G., & Chen, L. (2002) · Molecular Biotechnology · doi:10.1385/mb:21:3:259 · Cited by 12 · see citing works
Self-citationRole for peroxisome proliferator-activated receptor-gamma in Alzheimer's disease.
van Geel (2001) · Open Repository and Bibliography (University of Luxembourg) · doi:10.1002/1531-8249(20010201)49:2 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · see citing works
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628 · see citing works
Self-citationSafety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945 · see citing works
Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449 · see citing works
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198 · see citing works
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588 · see citing works
PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378 · see citing works
Elements of cancer immunity and the cancer–immune set point
Chen, D. S., & Mellman, I. (2017) · Nature · doi:10.1038/nature21349 · Cited by 5,352 · see citing works
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231 · see citing works
The biology and management of non-small cell lung cancer
Herbst, R. S., Morgensztern, D., & Boshoff, C. (2018) · Nature · doi:10.1038/nature25183 · Cited by 4,891 · see citing works
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878 · see citing works
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade
Postow, M. A., Sidlow, R., & Hellmann, M. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1703481 · Cited by 4,849 · see citing works
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229 · see citing works
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154 · see citing works
Rosenberg, J. E., Hoffman-Censits, J., Powles, T., van der Heijden, M. S., Balar, A. V., Necchi, A., Dawson, N., O'Donnell, P. H., Balmanoukian, A., Loriot, Y., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00561-4 · Cited by 3,669 · see citing works
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., Chen, Q., Gindin, M., Gubin, M. M., van der Windt, G. J. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.016 · Cited by 3,331 · see citing works
Brahmer, J. R., Drake, C. G., WOLLNER, I. S., Powderly, J. D., Picus, J., Sharfman, W. H., Stankevich, E., Pons, A., Salay, T. M., McMiller, T. L., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.7609 · Cited by 2,967 · see citing works
Self-citationExosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response
Chen, G., Huang, A. C., Zhang, W., Zhang, G., Wu, M., Xu, W., Yu, Z., Yang, J., Wang, B., Sun, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0392-8 · Cited by 2,813 · see citing works
Self-citationImmune Checkpoint Blockade in Cancer Therapy
Postow, M. A., Callahan, M. K., & Wolchok, J. D. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.4358 · Cited by 2,736 · see citing works
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.36 · Cited by 2,733 · see citing works
Weber, J. S., D’Angelo, S. P., Minor, D. R., Hodi, F. S., Gutzmer, R., Neyns, B., Höeller, C., Khushalani, N. I., Miller, W. H., Lao, C. D., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70076-8 · Cited by 2,676 · see citing works
Zou, W., Wolchok, J. D., & Chen, L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7118 · Cited by 2,382 · see citing works
Self-citationImmune checkpoint targeting in cancer therapy: toward combination strategies with curative potential
Sharma, P., & Allison, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.03.030 · Cited by 2,345 · see citing works
Taube, J. M., Klein, A., Brahmer, J. R., Xu, H., Pan, X., Kim, J. H., Chen, L., Pardoll, D. M., Topalian, S. L., & Anders, R. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3271 · Cited by 2,324 · see citing works
Self-citationGreenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318 · see citing works
PD-L1 expression as a predictive biomarker in cancer immunotherapy
Patel, S. P., & Kurzrock, R. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0983 · Cited by 2,291 · see citing works
Topalian, S. L., Sznol, M., McDermott, D. F., Kluger, H. M., Carvajal, R. D., Sharfman, W. H., Brahmer, J. R., Lawrence, D. P., Atkins, M. B., Powderly, J. D., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.0105 · Cited by 2,222 · see citing works
Non–Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment
Duma, N., Santana-Dávila, R., & Molina, J. R. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.01.013 · Cited by 2,218 · see citing works
Regulation and Function of the PD-L1 Checkpoint
Sun, C., Mezzadra, R., & Schumacher, T. N. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.014 · Cited by 2,187 · see citing works
Taube, J. M., Anders, R. A., Young, G. D., Xu, H., Sharma, R., McMiller, T. L., Chen, S., Klein, A. P., Pardoll, D. M., Topalian, S. L., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003689 · Cited by 2,157 · see citing works
Self-citationFeig, C., Jones, J. O., Kraman, M., Wells, R. J. B., Deonarine, A., Chan, D. S., Connell, C. M., Roberts, E. W., Zhao, Q., Caballero, O. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320318110 · Cited by 2,100 · see citing works
Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice
Deng, L., Liang, H. L., Burnette, B., Beckett, M., Darga, T. E., Weichselbaum, R. R., & Fu, Y. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67313 · Cited by 2,101 · see citing works
Natural Innate and Adaptive Immunity to Cancer
Vesely, M. D., Kershaw, M. H., Schreiber, R. D., & Smyth, M. J. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101324 · Cited by 2,095 · see citing works
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072 · see citing works
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells
Francisco, L. M., Salinas, V. H., Brown, K. E., Vanguri, V. K., Freeman, G. J., Kuchroo, V. K., & Sharpe, A. H. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090847 · Cited by 2,072 · see citing works
Immunosuppressive networks in the tumour environment and their therapeutic relevance
Zou, W. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1586 · Cited by 2,057 · see citing works
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
McLane, L. M., Abdel-Hakeem, M. S., & Wherry, E. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055318 · Cited by 1,973 · see citing works
Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression
Garcia-Diaz, A., Shin, D. S., Moreno, B. H., Saco, J., Escuin-Ordinas, H., Rodriguez, G. A., Zaretsky, J. M., Sun, L., Hugo, W., Wang, X., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.031 · Cited by 1,942 · see citing works
Ahmadzadeh, M., Johnson, L. A., Heemskerk, B., Wunderlich, J. R., Dudley, M. E., White, D. E., & Rosenberg, S. A. (2009) · Blood · doi:10.1182/blood-2008-12-195792 · Cited by 1,766 · see citing works
Butte, M. J., Keir, M. E., Phamduy, T. B., Sharpe, A. H., & Freeman, G. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.016 · Cited by 1,733 · see citing works
Immunosuppressive Strategies that are Mediated by Tumor Cells
Rabinovich, G. A., Gabrilovich, D. I., & Sotomayor, E. M. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141609 · Cited by 1,699 · see citing works
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689 · see citing works
Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608 · see citing works
Self-citationLlosa, N. J., Cruise, M., Tam, A., Wicks, E. C., Hechenbleikner, E. M., Taube, J. M., Blosser, R. L., Fan, H., Wang, H., Luber, B. S., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0863 · Cited by 1,487 · see citing works
Swann, J. B., & Smyth, M. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31405 · Cited by 1,469 · see citing works
Galectins as modulators of tumour progression
Liu, F., & Rabinovich, G. A. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1527 · Cited by 1,435 · see citing works
Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future
Chen, L., & Han, X. N. (2015) · Journal of Clinical Investigation · doi:10.1172/jci80011 · Cited by 1,433 · see citing works
Self-citationPD-L1 Expression in Triple-Negative Breast Cancer
Mittendorf, E. A., Philips, A. V., Meric‐Bernstam, F., Qiao, N., Wu, Y., Harrington, S. M., Su, X., Wang, Y., Gonzalez-Angulo, A. M., Akçakanat, A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0127 · Cited by 1,394 · see citing works
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization
Sanmamed, M. F., & Chen, L. (2018) · Cell · doi:10.1016/j.cell.2018.09.035 · Cited by 1,394 · see citing works
Self-citationHamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611533104 · Cited by 1,378 · see citing works
Cancer immunotherapy: harnessing the immune system to battle cancer
Yang, Y. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83871 · Cited by 1,366 · see citing works
Pitt, J. M., Marabelle, A., Eggermont, A. M. M., Soria, J., Kroemer, G., & Zitvogel, L. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw168 · Cited by 1,344 · see citing works
Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway
Boussiotis, V. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1514296 · Cited by 1,342 · see citing works
Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma
Parsa, A. T., Waldron, J. S., Panner, A., Crane, C. A., Parney, I. F., Barry, J. J., Cachola, K. E., Murray, J. C., Tihan, T., Jensen, M. C., et al. (2006) · Nature Medicine · doi:10.1038/nm1517 · Cited by 1,341 · see citing works
Arneth, B. M. (2019) · Medicina · doi:10.3390/medicina56010015 · Cited by 1,339 · see citing works
Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.12.009 · Cited by 1,324 · see citing works
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade
Dovedi, S. J., Adlard, A. L., Lipowska‐Bhalla, G., McKenna, C., Jones, S., Cheadle, E. J., Stratford, I. J., Poon, E., Morrow, M., Stewart, R. A., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1258 · Cited by 1,316 · see citing works
Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., et al. (2003) · Nature Medicine · doi:10.1038/nm863 · Cited by 1,314 · see citing works
Self-citationPD-1 and PD-1 ligands: from discovery to clinical application
Okazaki, T., & Honjo, T. (2007) · International Immunology · doi:10.1093/intimm/dxm057 · Cited by 1,310 · see citing works
Combination cancer immunotherapy and new immunomodulatory targets
Mahoney, K. M., Rennert, P. D., & Freeman, G. J. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4591 · Cited by 1,294 · see citing works
Gong, J., Chehrazi‐Raffle, A., Reddi, S., & Salgia, R. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0316-z · Cited by 1,279 · see citing works
Co-inhibitory molecules of the B7–CD28 family in the control of T-cell immunity
Chen, L. (2004) · Nature reviews. Immunology · doi:10.1038/nri1349 · Cited by 1,257 · see citing works
Self-citationKaufman, H. L., Russell, J., Hamid, O., Bhatia, S., Terheyden, P., D'Angelo, S. P., Shih, K. C., Lebbé, C., Linette, G. P., Milella, M., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30364-3 · Cited by 1,236 · see citing works
Hargadon, K. M., Johnson, C. E., & Williams, C. J. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.06.001 · Cited by 1,211 · see citing works
Immune checkpoint therapy—current perspectives and future directions
Sharma, P., Goswami, S., Raychaudhuri, D., Siddiqui, B. A., Singh, P., Nagarajan, A., Liu, J., Subudhi, S. K., Poon, C., Gant, K. L., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.006 · Cited by 1,206 · see citing works
Gettinger, S. N., Horn, L., Gandhi, L., Spigel, D. R., Antonia, S. J., Rizvi, N. A., Powderly, J. D., Heist, R. S., Carvajal, R. D., Jackman, D. M., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.58.3708 · Cited by 1,180 · see citing works
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target
Manguso, R. T., Pope, H. W., Zimmer, M. D., Brown, F. D., Yates, K. B., Miller, B. C., Collins, N. B., Bi, K., LaFleur, M. W., Juneja, V. R., et al. (2017) · Nature · doi:10.1038/nature23270 · Cited by 1,147 · see citing works
Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity
Li, C., Lim, S., Xia, W., Lee, H., Chan, L.-C., Kuo, C., Khoo, K., Chang, S.-S., Cha, J., Kim, T., et al. (2016) · Nature Communications · doi:10.1038/ncomms12632 · Cited by 1,100 · see citing works
Rosenwald, A., Wright, G. W., Leroy, K., Yu, X., Gaulard, P., Gascoyne, R. D., Chan, W. C., Zhao, T., Haïoun, C., Greiner, T. C., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20031074 · Cited by 1,095 · see citing works
Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial
Motzer, R. J., Rini, B. I., McDermott, D. F., Redman, B. G., Kuzel, T. M., Harrison, M. R., Vaishampayan, U. N., Drabkin, H. A., George, S., Logan, T. F., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.0703 · Cited by 1,074 · see citing works
Natural selection of tumor variants in the generation of “tumor escape” phenotypes
Khong, H. T., & Restifo, N. P. (2002) · Nature Immunology · doi:10.1038/ni1102-999 · Cited by 1,058 · see citing works
Mechanisms Controlling PD-L1 Expression in Cancer
Cha, J., Chan, L.-C., Li, C., Hsu, J. L., & Hung, M. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.030 · Cited by 1,054 · see citing works
Clinical implications of T cell exhaustion for cancer immunotherapy
Chow, A., Perica, K., Klebanoff, C. A., & Wolchok, J. D. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00689-z · Cited by 1,044 · see citing works
Pitt, J. M., Vétizou, M., Daillère, R., Roberti, M. P., Yamazaki, T., Routy, B., Lepage, P., Boneca, I. G., Chamaillard, M., Kroemer, G., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.06.001 · Cited by 1,040 · see citing works
Lung cancer: Biology and treatment options
Lemjabbar‐Alaoui, H., Hassan, O. U., Yang, Y., & Buchanan, P. C. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.08.002 · Cited by 1,024 · see citing works
Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity
Hirano, F., Kaneko, K., Tamura, H., Dong, H., Wang, S., Ichikawa, M., Rietz, C., Flies, D. B., Lau, J. S., Zhu, G., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.1089.65.3 · Cited by 1,018 · see citing works
Self-citationTargeting tumor-associated macrophages to synergize tumor immunotherapy
Xiang, X., Wang, J., Lu, D., & Xu, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00484-9 · Cited by 982 · see citing works
PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression
Jiao, S., Xia, W., Yamaguchi, H., Wei, Y., Chen, M.-K., Hsu, J.-M., Hsu, J. L., Yu, W.-H., Du, Y., Lee, H.-H., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3215 · Cited by 981 · see citing works
Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis
Conforti, F., Pala, L., Bagnardi, V., De Pas, T., Martinetti, M., Viale, G., Gelber, R. D., & Goldhirsch, A. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30261-4 · Cited by 973 · see citing works
Chen, L., Gibbons, D. L., Goswami, S., Cortez, M. A., Ahn, Y., Byers, L. A., Zhang, X., Yi, X., Dwyer, D. W., Lin, W., et al. (2014) · Nature Communications · doi:10.1038/ncomms6241 · Cited by 972 · see citing works
Self-citationExpression of Programmed Death 1 Ligands by Murine T Cells and APC
Yamazaki, T., Akiba, H., Iwai, H., Matsuda, H., Aoki, M., Tanno, Y., Shin, T., Tsuchiya, H., Pardoll, D. M., Okumura, K., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5538 · Cited by 950 · see citing works
Cancer nanomedicine for combination cancer immunotherapy
Nam, J., Son, S., Park, K. S., Zou, W., Shea, L. D., & Moon, J. J. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0108-1 · Cited by 946 · see citing works
Okazaki, T., Chikuma, S., Iwai, Y., Fagarasan, S., & Honjo, T. (2013) · Nature Immunology · doi:10.1038/ni.2762 · Cited by 915 · see citing works
Kuang, D., Zhao, Q., Peng, C., Xu, J., Zhang, J., Wu, C. Y., & Zheng, L. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082173 · Cited by 897 · see citing works
Kumagai, S., Koyama, S., Itahashi, K., Tanegashima, T., Lin, Y.-T., Togashi, Y., Kamada, T., Irie, T., Okumura, G., Kono, H., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.01.001 · Cited by 892 · see citing works
Clinical relevance of host immunity in breast cancer: from TILs to the clinic
Savas, P., Salgado, R., Denkert, C., Sotiriou, C., Darcy, P. K., Smyth, M. J., & Loi, S. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.215 · Cited by 890 · see citing works
Nomi, T., Sho, M., Akahori, T., Hamada, K., Kubo, A., Kanehiro, H., Nakamura, S., Enomoto, K., Yagita, H., Azuma, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2746 · Cited by 889 · see citing works
PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection
Petrovas, C., Casazza, J. P., Brenchley, J. M., Price, D. A., Gostick, E., Adams, W. C., Precopio, M. L., Schacker, T., Roederer, M., Douek, D. C., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061496 · Cited by 889 · see citing works
Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3
Wang, J., Sanmamed, M. F., Datar, I. J., Su, T. T., Ji, L., Sun, J., Chen, L., Chen, Y., Zhu, G., Yin, W., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.010 · Cited by 879 · see citing works
Self-citationThompson, R. H., Kuntz, S. M., Leibovich, B. C., Dong, H., Lohse, C. M., Webster, W. S., Sengupta, S., Frank, I., Parker, A. S., Zincke, H., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4303 · Cited by 869 · see citing works
Self-citationRegulatory mechanisms of PD-1/PD-L1 in cancers
Lin, X., Kang, K., Chen, P., Zeng, Z., Li, G., Xiong, W., Yi, M., & Xiang, B. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02023-w · Cited by 850 · see citing works
Juneja, V. R., McGuire, K. A., Manguso, R. T., LaFleur, M. W., Collins, N. B., Haining, W. N., Freeman, G. J., & Sharpe, A. H. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160801 · Cited by 848 · see citing works
Chen, B. J., Chapuy, B., Ouyang, J., Sun, H. H., Roemer, M. G. M., Xu, M. L., Yu, H., Fletcher, C. D. �., Freeman, G. J., Shipp, M. A., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0855 · Cited by 839 · see citing works
Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer
McLaughlin, J. F., Han, G., Schalper, K. A., Carvajal‐Hausdorf, D., Pelekanou, V., Rehman, J., Velcheti, V., Herbst, R. S., LoRusso, P. M., & Rimm, D. L. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.3638 · Cited by 835 · see citing works
The Programmed Death-1 (PD-1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice
Ansari, M. J., Salama, A. D., Chitnis, T., Smith, R. N., Yagita∥, H., Akiba, H., Yamazaki, T., Azuma, M., Iwai, H., Khoury, S. J., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022125 · Cited by 806 · see citing works
Ohigashi, Y., Sho, M., Yamada, Y., Tsurui, Y., Hamada, K., Ikeda, N., Mizuno, T., Yoriki, R., Kashizuka, H., Yane, K., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1469 · Cited by 796 · see citing works
The changing therapeutic landscape of head and neck cancer
Cramer, J. D., Burtness, B. A., Le, Q., & Ferris, R. L. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0227-z · Cited by 794 · see citing works
Kumagai, S., Togashi, Y., Kamada, T., Sugiyama, E., Nishinakamura, H., Takeuchi, Y., Kochin, V., Itahashi, K., Maeda, Y., Matsui, S., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0769-3 · Cited by 794 · see citing works
Deubiquitination and Stabilization of PD-L1 by CSN5
Lim, S.-O., Li, C.-W., Xia, W., Cha, J.-H., Chan, L.-C., Wu, Y., Chang, S.-S., Lin, W.-C., Hsu, J.-M., Hsu, Y.-H., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.10.010 · Cited by 793 · see citing works
PD-L1 expression in human cancers and its association with clinical outcomes
Yu, J., Wang, X., Teng, F., & Kong, L. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s105862 · Cited by 787 · see citing works
- Authors
- Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., Lennon, V. A., Celis, E., & Chen, L.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Chen, Lieping
- ORCID
- Venue
- Nature Medicine
- Published
- 2002-06-24
- Volume
- 8
- Issue
- 8
- Pages
- 793-800
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2016983859
- Cited by
- 5,025
- References
- 39
- Citations by year
- 2026: 162 · 2025: 222 · 2024: 250 · 2023: 298 · 2022: 296 · 2021: 367 · 2020: 377 · 2019: 388 · 2018: 424 · 2017: 406 · 2016: 364 · 2015: 316 · 2014: 175 · 2013: 178 · 2012: 106
- FWCI
- 24.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA037343, CA-85721, CA79915, CA82677, CA-37343, R01CA079915, R01CA080782, CA80782, R01CA082677, R01CA085721, CA 15083, P30CA015083)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- PD-L1, T cell apoptosis, immune evasion, PD-1 receptor, interferon-gamma, costimulatory molecules, tumor immunogenicity, melanoma, lung cancer, ovarian carcinoma, colon cancer
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigens, Surface, Antineoplastic Agents, Blood Proteins, Cell Separation, Female, Flow Cytometry, Humans, Lymphocyte Activation, Melanoma, Membrane Glycoproteins, Mice, Inbred Strains, Neoplasms, Peptides, Recombinant Fusion Proteins, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Signal Transduction, Antigens, CD, Apoptosis, B7-1 Antigen, Tumor Escape, Apoptosis Regulatory Proteins, Mice, TNF-Related Apoptosis-Inducing Ligand, Fas Ligand Protein, B7-H1 Antigen, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review