Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation
Open accessAbstract
PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.
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PD-L1 (CD274) interacts with the PD-1 receptor on T cells to inhibit T-cell activation.
“the inhibitory immune checkpoint CD274 (also known as PD-L1), which interacts with the PD-1 receptor on T cells to inhibit T-cell activation [5]”
From Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens (2021) · cites this paper as [5]
PD-1 activity is only relevant during simultaneous T cell activation, as its signal transduction only comes into effect during TCR-dependent signaling.
“PD-1 activity is therefore only relevant during simultaneous T cell activation, as its signal transduction can only come into effect during TCR-dependent signaling (39, 41, 48).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [48]
PD-1 interaction with PD-L1 and PD-L2 can diminish immune responses.
“Upon interaction with its ligands, programmed death-ligand 1 (PD-L1; a.k.a. B7-H1 or CD274) and PD-L2 (a.k.a. B7-DC or CD273), it can diminish immune responses (Freeman et al., 2000; Latchman et al., 2001).”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Freeman et al., 2000
Engagement of PD-1 with PD-L1 or PD-L2 suppresses T cell immune responses.
“Similar to CTLA-4, engagement of PD-1 with its ligands, PD-L1 and PD-L2, leads to suppression of T cell immune responses (36,37).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [36]
PD-L1 and PD-L2 are expressed on hematopoietic and nonhematopoietic cells, including APCs and cancer cells.
“Both PD-L1 and PD-L2 are expressed on hematopoietic and nonhematopoietic cells, including APCs and cancer cells (36,37).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [36]
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Cites
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
Self-citationTivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914 · see citing works
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in <i>Ctla-4</i>
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766 · 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
Self-citationDong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496 · see citing works
Suda, T., Takahashi, T., Golstein, P., & Nagata, S. (1993) · Cell · doi:10.1016/0092-8674(93)90326-l · Cited by 2,488 · 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
Self-citationT-cell co-stimulation through B7RP-1 and ICOS
Yoshinaga, S. K., Whoriskey, J. S., Khare, S. D., Sarmiento, U. M., Guo, J., Horan, T., Shih, G. C., Zhang, M., Coccia, M. A., Kohno, T., et al. (1999) · Nature · doi:10.1038/45582 · Cited by 775 · see citing works
The Emerging Role of CTLA-4 as an Immune Attenuator
Thompson, C. B., & Allison, J. P. (1997) · Immunity · doi:10.1016/s1074-7613(00)80366-0 · Cited by 633 · see citing works
Nishimura, H. (1998) · International Immunology · doi:10.1093/intimm/10.10.1563 · Cited by 500 · see citing works
Self-citationB7h, a Novel Costimulatory Homolog of B7.1 and B7.2, Is Induced by TNFα
Swallow, M. M., Wallin, J. J., & Sha, W. C. (1999) · Immunity · doi:10.1016/s1074-7613(00)80117-x · Cited by 453 · see citing works
Harper, K., Balzano, C., Rouvier, É., Mattéi, M., Luciani, M., & Golstein, P. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.3.1037 · Cited by 432 · see citing works
Immunoreceptor tyrosine-based inhibition motifs
Vivier, É., & Daëron, M. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)80025-4 · Cited by 388 · see citing works
Freedman, A. S., Freeman, G. J., Rhynhart, K. K., & Nadler, L. M. (1991) · Cellular Immunology · doi:10.1016/0008-8749(91)90091-o · Cited by 312 · see citing works
Self-citationStructure and Chromosomal Localization of the Human PD-1 Gene (PDCD1)
Shinohara, T., Taniwaki, M., Ishida, Y., Kawaichi, M., & Honjo, T. (1994) · Genomics · doi:10.1006/geno.1994.1562 · Cited by 255 · see citing works
Self-citationStructure and Dimerization of a Soluble Form of B7-1
Ikemizu, S., Gilbert, R. J. C., Fennelly, J. A., Collins, A. V., Harlos, K., Jones, E. Y., Stuart, D. I., & Davis, S. J. (2000) · Immunity · doi:10.1016/s1074-7613(00)80158-2 · Cited by 249 · see citing works
Ling, V., Wu, P. W., Finnerty, H. F., Bean, K. M., Spaulding, V., Fouser, L. A., Leonard, J. P., HUNTER, S. E., Zollner, R. S., Thomas, J. L., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.4.1653 · Cited by 230 · see citing works
Self-citationBoussiotis, V. A., Freeman, G. J., Grffiben, J. G., & Nadler, L. M. (1996) · Immunological Reviews · doi:10.1111/j.1600-065x.1996.tb00918.x · Cited by 155 · see citing works
Self-citationActivation-Induced Expression of Human Programmed Death-1 Gene in T-Lymphocytes
Vibhakar, R., Juan, G., Traganos, F., Darżynkiewicz, Z., & Finger, L. R. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3493 · Cited by 149 · see citing works
The Complexities of T‐Cell Co‐stimulation: CD28 and Beyond
Sperling, A. I., & Bluestone, J. A. (1996) · Immunological Reviews · doi:10.1111/j.1600-065x.1996.tb00924.x · Cited by 147 · see citing works
Blair, P. J., Riley, J. L., Levine, B. L., Lee, K. P., Craighead, N., Francomano, T., Perfetto, S. J., Gray, G. S., Carreno, B. M., & June, C. H. (1998) · PubMed · Cited by 135 · see citing works
Self-citationStructure and evolution of the extended B7 family
Henry, J., Miller, M. M., & Pontarotti, P. (1999) · Immunology Today · doi:10.1016/s0167-5699(98)01418-2 · Cited by 108 · see citing works
Nickoloff, B. J., Mitra, R. S., Lee, K., et al. (1993) · PubMed · Cited by 101 · see citing works
Freeman, G. J., Cardoso, A. A., Boussiotis, V. A., Anumanthan, A., Groves, R. W., Kupper, T. S., Clark, E. A., & Nadler, L. M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.6.2708 · Cited by 45 · see citing works
Self-citationCharacterization of murine Flt4 ligand/VEGF-C
Fitz, L. J., Morris, J. C., Towler, P., et al. (1997) · Oncogene · doi:10.1038/sj.onc.1201191 · Cited by 44 · see citing works
Self-citationThe costimulatory genes Cd80 and Cd86 are linked on mouse chromosome 16 and human chromosome 3
Reeves, R. H., Patch, D., Sharpe, A. H., et al. (1997) · Mammalian Genome · doi:10.1007/s003359900508 · Cited by 15 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Byrne M.C. Whitley M.Z. Follettie M.T. Preparation of mRNA for expression monitoring Ausubel F.M. Brent R. Kingston R.E. Moore D.D. Seidman J.G. Smith J.A. Struhl K. Current Protocols in Molecular Biology Supplement. Vol. 49 2000 22 John Wiley & Sons, Inc New York2.1–22.2.13.
- Freeman G.J. Lombard D.B. Gimmi C.D. Brod S.A. Lee K. Laning J.C. Hafler D.A. Dorf M.E. Gray G.S. Reiser H. CTLA-4 and CD28 are coexpressed in most T-cells after activation J. Immunol. 149 1992 3795 3801 1281186
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
Safety 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
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
Self-citationTumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025 · 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
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
Top 10 Challenges in Cancer Immunotherapy
Hegde, P. S., & Chen, D. S. (2020) · Immunity · doi:10.1016/j.immuni.2019.12.011 · Cited by 2,238 · see citing works
Immune 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
PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Gordon, S. R., Maute, R. L., Dulken, B. W., Hutter, G., George, B. M., McCracken, M. N., Gupta, R., Tsai, J. M., Sinha, R., Corey, D., et al. (2017) · Nature · doi:10.1038/nature22396 · Cited by 2,247 · see citing works
Bagchi, S., Yuan, R., & Engleman, E. G. (2021) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-042020-042741 · Cited by 2,189 · 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
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
Fuchs, C. S., Doi, T., Jang, R. W., Muro, K., Satoh, T., Machado, M., Sun, W., Jalal, S. I., Shah, M. A., Metges, J.-P., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.0013 · Cited by 1,784 · 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
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648 · see citing works
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer
Costa, A., Kieffer, Y., Scholer-Dahirel, A., Pelon, F., Bourachot, B., Cardon, M., Sirven, P., Magagna, I., Fuhrmann, L., Bernard, C., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.011 · Cited by 1,705 · 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
Lei, X., Lei, Y., Li, J.-K., Du, W.-X., Li, R.-G., Yang, J., Li, J., Li, F., & Tan, H.-B. (2020) · Cancer Letters · doi:10.1016/j.canlet.2019.11.009 · Cited by 1,470 · see citing works
Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
Trautmann, L., Janbazian, L., Chomont, N., Said, E. A., Gimmig, S., Bessette, B., Boulassel, M.-R., Delwart, E., Sepulveda, H., Balderas, R. S., et al. (2006) · Nature Medicine · doi:10.1038/nm1482 · Cited by 1,565 · see citing works
Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations
Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360 · see citing works
Hamanishi, 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
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
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302 · 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
Yokosuka, T., Takamatsu, M., Kobayashi-Imanishi, W., Hashimoto-Tane, A., Azuma, M., & Saito, T. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112741 · Cited by 1,161 · see citing works
Barroso-Sousa, R., Barry, W. T., Garrido-Castro, A. C., Hodi, F. S., Min, L., Krop, I. E., & Tolaney, S. M. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2017.3064 · Cited by 1,115 · see citing works
Lv, M., Chen, M., Zhang, R., Zhang, W., Wang, C., Zhang, Y., Wei, X., Guan, Y., Liu, J., Feng, K., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00395-4 · Cited by 1,040 · 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
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
Brown, J. A., Dorfman, D. M., Ma, F.-R., Sullivan, E. L., Munoz, O., Wood, C. R., Greenfield, E. A., & Freeman, G. J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.3.1257 · Cited by 968 · see citing works
Self-citationNomi, 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
BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1
Watanabe, N., Gavrieli, M., Sedy, J. R., Yang, J., Fallarino, F., Loftin, S. K., Hurchla, M. A., Zimmerman, N., Sim, J., Zang, X., et al. (2003) · Nature Immunology · doi:10.1038/ni944 · Cited by 883 · 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
A major chromatin regulator determines resistance of tumor cells to T cell–mediated killing
Pan, D., Kobayashi, A., Jiang, P., Ferrari de Andrade, L., Tay, R. E., Luoma, A. M., Tsoucas, D., Qiu, X., Lim, K., Rao, P., et al. (2018) · Science · doi:10.1126/science.aao1710 · Cited by 852 · see citing works
Sheppard, K.-A., Fitz, L. J., Lee, J. M., Benander, C., George, J. A., Wooters, J., Qiu, Y., Jussif, J. M., Carter, L. L., Wood, C. R., et al. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.07.083 · Cited by 791 · see citing works
Self-citationGettinger, S., Choi, J., Hastings, K., Truini, A., Datar, I., Sowell, R., Wurtz, A., Dong, W., Cai, G., Melnick, M. A., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0593 · Cited by 787 · 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
Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy
Highfill, S. L., Cui, Y., Giles, A. J., Smith, J. P., Zhang, H., Morse, E., Kaplan, R. N., & Mackall, C. L. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007974 · Cited by 767 · see citing works
“Signaling of PD1 on T cells via PD-L1 (B7-H1) or PD-L2 (B7-DC) inhibits T cell receptor–mediated activation by recruitment of the SHP2 phosphatase (2).”
BackgroundIFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer
Abiko, K., Matsumura, N., Hamanishi, J., Horikawa, N., Murakami, R., Yamaguchi, K., Yoshioka, Y., Baba, T., Konishi, I., & Mandai, M. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.101 · Cited by 725 · see citing works
Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer
Wing, J. B., Tanaka, A., & Sakaguchi, S. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.020 · Cited by 726 · see citing works
Yang, H., Bueso-Ramos, C., DiNardo, C., Estecio, M. R., Davanlou, M., Geng, Q.-R., Fang, Z., Nguyen, M., Pierce, S., Wei, Y., et al. (2014) · Leukemia · doi:10.1038/leu.2013.355 · Cited by 688 · see citing works
Cancer immunotherapy—immune checkpoint blockade and associated endocrinopathies.
Byun, D. J., Wolchok, J. D., Rosenberg, L. M., & Girotra, M. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.205 · Cited by 685 · see citing works
Daud, A. I., Wolchok, J. D., Robert, C., Hwu, W.-J., Weber, J. S., Ribas, A., Hodi, F. S., Joshua, A. M., Kefford, R., Hersey, P., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.2477 · Cited by 665 · see citing works
TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.013 · Cited by 656 · see citing works
“lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) (Freeman et al., 2000; Leach et al., 1996).”
Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles
Ricklefs, F. L., Alayo, Q., Krenzlin, H., Mahmoud, A. B., Speranza, M. C., Nakashima, H., Hayes, J. L., Lee, K., Balaj, L., Passaro, C., et al. (2018) · Science Advances · doi:10.1126/sciadv.aar2766 · Cited by 610 · see citing works
Self-citationThe PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation
Bardhan, K., Anagnostou, T., & Boussiotis, V. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00550 · Cited by 606 · see citing works
Gao, J., Ward, J. F., Pettaway, C. A., Shi, L. Z., Subudhi, S. K., Vence, L. M., Zhao, H., Chen, J., Chen, H., Efstathiou, E., et al. (2017) · Nature Medicine · doi:10.1038/nm.4308 · Cited by 594 · see citing works
The B7 family member B7-H3 preferentially down-regulates T helper type 1–mediated immune responses
Suh, W.-K., Gajewska, B. U., Okada, H., Gronski, M. A., Bertram, E. M., Dawicki, W., Duncan, G. S., Bukczynski, J., Plyte, S., Elia, A., et al. (2003) · Nature Immunology · doi:10.1038/ni967 · Cited by 576 · see citing works
Weber, J. S., Kudchadkar, R. R., Yu, B., Gallenstein, D., Horak, C. E., Inzunza, H. D., Zhao, X., Martinez, A. J., Wang, W., Gibney, G., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.51.4802 · Cited by 535 · see citing works
Cotton, A. D., Nguyen, D. P., Gramespacher, J. A., Seiple, I. B., & Wells, J. A. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.0c10008 · Cited by 551 · see citing works
Patsoukis, N., Brown, J., Petkova, V., Liu, F., Li, L., & Boussiotis, V. A. (2012) · Science Signaling · doi:10.1126/scisignal.2002796 · Cited by 529 · see citing works
Kinter, A. L., Godbout, E. J., McNally, J. P., Sereti, I., Roby, G. A., O’Shea, M. A., & Fauci, A. S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.6738 · Cited by 513 · see citing works
Jiang, X., Zhou, J., Giobbie-Hurder, A., Wargo, J., & Hodi, F. S. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2731 · Cited by 485 · see citing works
Groeger, S., & Meyle, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00208 · Cited by 473 · see citing works
Nakanishi, J., Wada, Y., Matsumoto, K., Azuma, M., Kikuchi, K., & Ueda, S. (2007) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-006-0266-z · Cited by 473 · see citing works
PD‐1/PD‐L1 pathway: Basic biology and role in cancer immunotherapy
Salmaninejad, A., Valilou, S. F., Shabgah, A. G., Aslani, S., Alimardani, M., Pasdar, A., & Sahebkar, A. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28358 · Cited by 445 · see citing works
Role of the PD-1 pathway in the immune response
Riella, L. V., Paterson, A. M., Sharpe, A. H., & Chandraker, A. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04224.x · Cited by 444 · see citing works
“PD-L1 is expressed constitutively on murine T and B cells, DCs, macrophages, mesenchymal stem cells and bone marrow-derived mast cells (12,18), and induced to higher levels by inflammation.”
BackgroundThe emerging role of epigenetic therapeutics in immuno-oncology
Topper, M. J., Vaz, M., Marrone, K. A., Brahmer, J. R., & Baylin, S. B. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0266-5 · Cited by 433 · see citing works
Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor
Belum, V. R., Benhuri, B., Postow, M. A., Hellmann, M. D., Lesokhin, A. M., Segal, N. H., Motzer, R. J., Wu, S., Busam, K. J., Wolchok, J. D., et al. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2016.02.010 · Cited by 418 · see citing works
Zhao, Y., Lee, C. K., Lin, C.-H., Gassen, R. B., Xu, X., Huang, Z., Xiao, C., Bonorino, C., Lu, L.-F., Bui, J. D., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.11.003 · Cited by 383 · see citing works
Baessler, A., & Vignali, D. A. A. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-110914 · Cited by 420 · see citing works
Immune modulation by mesenchymal stem cells
Rasmusson, I. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.03.019 · Cited by 374 · see citing works
Mühlbauer, M., Fleck, M., Schütz, C., Weiss, T., Froh, M., Blank, C., Schölmerich, J., & Hellerbrand, C. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.05.007 · Cited by 378 · see citing works
Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses
Liu, J., Yuan, Y., Chen, W., Putra, J., Suriawinata, A. A., Schenk, A. D., Miller, H. E., Guleria, I., Barth, R. J., Huang, Y. H., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1420370112 · Cited by 374 · see citing works
Murine B7-H3 is a negative regulator of T cells
Prasad, D. V. R., Nguyen, T., Li, Z., Yang, Y., Duong, J., Wang, Y., & Dong, C. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.4.2500 · Cited by 368 · see citing works
PD-1 is a novel regulator of human B-cell activation
Thibult, M.-L., Mamessier, E., Gertner-Dardenne, J., Pastor, S., Just-Landi, S., Xerri, L., Chetaille, B., & Olive, D. (2013) · International Immunology · doi:10.1093/intimm/dxs098 · Cited by 365 · see citing works
p53, cancer and the immune response
Blagih, J., Buck, M. D., & Vousden, K. H. (2020) · Journal of Cell Science · doi:10.1242/jcs.237453 · Cited by 333 · see citing works
Constantinidou, A., Alifieris, C., & Trafalis, D. T. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.09.008 · Cited by 342 · see citing works
Liu, Y., Zugazagoitia, J., Ahmed, F. S., Henick, B. S., Gettinger, S. N., Herbst, R. S., Schalper, K. A., & Rimm, D. L. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1040 · Cited by 322 · see citing works
Bellucci, R., Martin, A., Bommarito, D., Wang, K., Hansen, S. H., Freeman, G. J., & Ritz, J. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1008824 · Cited by 307 · see citing works
Self-citationLenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma
Görgün, G., Samur, M. K., Cowens, K. B., Paula, S., Bianchi, G., Anderson, J. E., White, R. E., Singh, A., Ohguchi, H., Suzuki, R., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0200 · Cited by 309 · see citing works
Gok Yavuz, B., Gunaydin, G., Gedik, M. E., Kosemehmetoglu, K., Karakoc, D., Ozgur, F., & Guc, D. (2019) · Scientific Reports · doi:10.1038/s41598-019-39553-z · Cited by 292 · see citing works
Inhibition of T–Cell Responses by Hepatic Stellate Cells Via B7–H1-Mediated T–Cell Apoptosis in Mice
Yu, M., Chen, C., Liang, X., Wang, L., Gandhi, C. R., Fung, J. J., Lu, L., & Qian, S. (2004) · Hepatology · doi:10.1002/hep.20488 · Cited by 301 · see citing works
Blockade of PD‐L1 (B7‐H1) augments human tumor‐specific T cell responses <i>in vitro</i>
Blank, C., Kuball, J., Voelkl, S., Wiendl, H., Becker, B., Walter, B., Majdic, O., Gajewski, T. F., Theobald, M., Andreesen, R., et al. (2006) · International Journal of Cancer · doi:10.1002/ijc.21775 · Cited by 297 · see citing works
Diehl, L., Schurich, A., Grochtmann, R., Hegenbarth, S., Chen, L., & Knolle, P. A. (2008) · Hepatology · doi:10.1002/hep.21965 · Cited by 291 · see citing works
Obesity accelerates T cell senescence in murine visceral adipose tissue
Shirakawa, K., Yan, X., Shinmura, K., Endo, J., Kataoka, M., Katsumata, Y., Yamamoto, T., Anzai, A., Isobe, S., Yoshida, N., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci88606 · Cited by 271 · see citing works
Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells
Eppihimer, M., Gunn, J., Freeman, G., Greenfield, E., Chernova, T., Erickson, J., & Leonard, J. (2002) · Microcirculation · doi:10.1080/713774061 · Cited by 272 · see citing works
Self-citationAugmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold
Vredevoogd, D. W., Kuilman, T., Ligtenberg, M. A., Boshuizen, J., Stecker, K. E., de Bruijn, B., Krijgsman, O., Huang, X., Kenski, J. C. N., Lacroix, R., et al. (2019) · Cell · doi:10.1016/j.cell.2019.06.014 · Cited by 259 · see citing works
Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review
Kumar, A., Gautam, V., Sandhu, A., Rawat, K., Sharma, A., & Saha, L. (2023) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v15.i4.495 · Cited by 272 · see citing works
Papalexi, E., Mimitou, E. P., Butler, A. W., Foster, S., Bracken, B., Mauck, W. M., Wessels, H.-H., Hao, Y., Yeung, B. Z., Smibert, P., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00778-2 · Cited by 238 · see citing works
Pance, K., Gramespacher, J. A., Byrnes, J. R., Salangsang, F., Serrano, J.-A. C., Cotton, A. D., Steri, V., & Wells, J. A. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01456-2 · Cited by 265 · see citing works
Nazareth, M. R., Broderick, L., Simpson-Abelson, M. R., Kelleher, R. J., Yokota, S. J., & Bankert, R. B. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5552 · Cited by 259 · see citing works
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237 · see citing works
Hudson, K., Cross, N., Jordan-Mahy, N., & Leyland, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.568931 · Cited by 243 · see citing works
Nielsen, C., Hansen, D., Husby, S., Jacobsen, B. B., & Lillevang, S. T. (2003) · Tissue Antigens · doi:10.1046/j.1399-0039.2003.00136.x · Cited by 232 · see citing works
Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor suppression
Hossain, D. M. S., Javaid, S., Cai, M., Zhang, C., Sawant, A., Hinton, M., Sathe, M., Grein, J., Blumenschein, W., Pinheiro, E. M., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci94586 · Cited by 216 · see citing works
Molecular pathways and therapeutic targets in lung cancer
Shtivelman, E., Hensing, T., Simon, G. R., Dennis, P. A., Otterson, G. A., Bueno, R., & Salgia, R. (2014) · Oncotarget · doi:10.18632/oncotarget.1891 · Cited by 220 · see citing works
“Interactions between PD-1 and its ligands attenuate immune responses [241], and, in the context of cancer, serve to protect tumor cells from cytotoxic T cells.”
BackgroundB7-H1-Induced Apoptosis as a Mechanism of Immune Privilege of Corneal Allografts
Hori, J., Wang, M., Miyashita, M., Tanemoto, K., Takahashi, H., Takemori, T., Okumura, K., Yagita, H., & Azuma, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.5928 · Cited by 208 · see citing works
Wang, Y., Zhang, L., Xu, Z., Miao, L., & Huang, L. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.11.009 · Cited by 206 · see citing works
Sallman, D. A., McLemore, A. F., Aldrich, A. L., Komrokji, R. S., McGraw, K. L., Dhawan, A., Geyer, S., Hou, H.-A., Eksioglu, E. A., Sullivan, A., et al. (2020) · Blood · doi:10.1182/blood.2020006158 · Cited by 196 · see citing works
Metcalf, T. U., Cubas, R. A., Ghneim, K., Cartwright, M. J., Grevenynghe, J. V., Richner, J. M., Olagnier, D. P., Wilkinson, P. A., Cameron, M. J., Park, B. S., et al. (2015) · Aging Cell · doi:10.1111/acel.12320 · Cited by 189 · see citing works
Knudson, K. M., Hicks, K. C., Luo, X., Chen, J.-Q., Schlom, J., & Gameiro, S. R. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1426519 · Cited by 195 · see citing works
Development of an automated PD-L1 immunohistochemistry (IHC) assay for non-small cell lung cancer
Phillips, T., Simmons, P., Inzunza, H. D., Cogswell, J., Novotny, J., Taylor, C., & Zhang, X. (2015) · Applied Immunohistochemistry & Molecular Morphology · doi:10.1097/pai.0000000000000256 · Cited by 189 · see citing works
Subrahmanyam, P. B., Dong, Z., Gusenleitner, D., Giobbie-Hurder, A., Severgnini, M., Zhou, J., Manos, M., Eastman, L. M., Maecker, H. T., & Hodi, F. S. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0328-8 · Cited by 190 · see citing works
Dovedi, S. J., Elder, M. J., Yang, C., Sitnikova, S. I., Irving, L., Hansen, A., Hair, J., Jones, D. C., Hasani, S., Wang, B., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1445 · Cited by 186 · see citing works
PD-1 expression on dendritic cells suppresses CD8<sup>+</sup>T cell function and antitumor immunity
Lim, T. S., Chew, V., Sieow, J. L., Goh, S., Yeong, J. P.-S., Soon, A. L., & Ricciardi-Castagnoli, P. (2016) · OncoImmunology · doi:10.1080/2162402x.2015.1085146 · Cited by 184 · see citing works
David, J. M., Dominguez, C., McCampbell, K. K., Gulley, J. L., Schlom, J., & Palena, C. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1349589 · Cited by 180 · see citing works
- Authors
- Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., Horton, H. F., Fouser, L., Carter, L., Ling, V., Bowman, M. R., Carreno, B. M., Collins, M., Wood, C. R., & Honjo, T.
- Affiliations
- Harvard University (US)
- bGenetics Institute, Wyeth-Ayerst Research, Cambridge, Massachusetts 02140
- Kyoto University (JP)
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2000-10-02
- Volume
- 192
- Issue
- 7
- Pages
- 1027-1034
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2193311
- OpenAlex
- W2118471749
- Cited by
- 5,294
- References
- 26
- Citations by year
- 2026: 147 · 2025: 255 · 2024: 298 · 2023: 328 · 2022: 357 · 2021: 454 · 2020: 451 · 2019: 391 · 2018: 386 · 2017: 375 · 2016: 279 · 2015: 267 · 2014: 158 · 2013: 163 · 2012: 109
- FWCI
- 18.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Seerave Foundation
- E-Rare
- European Commission
- Agence Nationale de la Recherche (ANR-16-RHUS-0008)
- Fondation Leducq
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Institut Universitaire de France
- Institut National Du Cancer
- National Institutes of Health (5p01ai041584-05)
- Horizon 2020 Framework Programme (GDW20171100085, GDW20181100051)
- High-end Foreign Experts Recruitment Plan of China (GDW20171100085, GDW20181100051)
- Labex Immuno-Oncology
- National Cancer Institute (CA 84500, R01CA084500)
- National Institute of Allergy and Infectious Diseases (AI 39671, AI 41584, P01AI039671)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- PD-1, PD-L1, B7 family, T cell activation, lymphocyte proliferation, cytokine production, CD28 costimulation, antigen-presenting cells, dendritic cells, monocytes, interferon-gamma, autoimmunity, peripheral tolerance
- MeSH terms
- Amino Acid Sequence, Animals, Antigen-Presenting Cells, Antigens, Surface, Base Sequence, Cell Division, Humans, Ligands, Membrane Glycoproteins, Molecular Sequence Data, T-Lymphocytes, Signal Transduction, Antigens, CD, Gene Expression, CD3 Complex, DNA, Complementary, CD28 Antigens, B7-1 Antigen, Apoptosis Regulatory Proteins, Mice, B7-2 Antigen, Programmed Cell Death 1 Receptor
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