Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production
Abstract
Programmed death-1 ligand (PD-L)1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells. PD-1 contains an immunoreceptor tyrosine-based inhibitory motif and mice deficient in PD-1 develop autoimmune disorders suggesting a defect in peripheral tolerance. Human PD-L1 and PD-L2 are expressed on immature dendritic cells (iDC) and mature dendritic cells (mDC), IFN-gamma-treated monocytes, and follicular dendritic cells. Using mAbs, we show that blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. Enhancement of T cell activation was most pronounced with weak APC, such as iDCs and IL-10-pretreated mDCs, and less pronounced with strong APC such as mDCs. These data are consistent with the hypothesis that iDC have a balance of stimulatory vs inhibitory molecules that favors inhibition, and indicate that PD-L1 and PD-L2 contribute to the poor stimulatory capacity of iDC. PD-L1 expression differs from PD-L2 in that PD-L1 is expressed on activated T cells, placental trophoblasts, myocardial endothelium, and cortical thymic epithelial cells. In contrast, PD-L2 is expressed on placental endothelium and medullary thymic epithelial cells. PD-L1 is also highly expressed on most carcinomas but minimally expressed on adjacent normal tissue suggesting a role in attenuating antitumor immune responses.
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IFN-γ is the main trigger known to cause PD-L1 and PD-L2 upregulation.
“Interferon (IFN)-γ is the main trigger known to cause PD-L1 and PD-L2 upregulation (41).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [41]
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 [41]
Cites
Dendritic cells and the control of immunity
Banchereau, J., & Steinman, R. M. (1998) · Nature · doi:10.1038/32588 · Cited by 14,244 · see citing works
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
Self-citationIshida, 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
Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,204 · see citing works
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955 · see citing works
Self-citationNishimura, 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
Dong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496 · see citing works
Antigen presentation and T cell stimulation by dendritic cells.
Guermonprez, P., Valladeau, J., Zitvogel, L., Théry, C., & Amigorena, S. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064828 · Cited by 2,106 · 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
Sharpe, A. H., & Freeman, G. J. (2002) · Nature reviews. Immunology · doi:10.1038/nri727 · Cited by 1,713 · see citing works
Self-citationExpression 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
Jonuleit, H., Schmitt, E., Schuler, G., Knop, J., & Enk, A. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.9.1213 · Cited by 1,538 · see citing works
Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Münz, C., & Bhardwaj, N. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.2.233 · Cited by 1,359 · see citing works
Induction of tolerance by IL-10-treated dendritic cells
Steinbrink, K., Wölfl, M., Jonuleit, H., Knop, J., & Enk, A. H. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.10.4772 · Cited by 1,245 · see citing works
Chambers, C. A., Kuhns, M. S., Egen, J. G., & Allison, J. P. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.565 · Cited by 1,000 · see citing works
B7-Dc, a New Dendritic Cell Molecule with Potent Costimulatory Properties for T Cells
Tseng, S.-Y., Otsuji, M., Gorski, K. S., Huang, X., Slansky, J. E., Pai, S. I., Shalabi, A., Shin, T., Pardoll, D. M., & Tsuchiya, H. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.7.839 · Cited by 867 · see citing works
Okazaki, T., Maeda, A., Nishimura, H., Kurosaki, T., & Honjo, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231486598 · Cited by 849 · see citing works
The Interaction Properties of Costimulatory Molecules Revisited
Collins, A. V., Brodie, D. W., Gilbert, R. J. C., Iaboni, A., Manso-Sancho, R., Walse, B., Stuart, D. I., van der Merwe, P. A., & Davis, S. J. (2002) · Immunity · doi:10.1016/s1074-7613(02)00362-x · Cited by 684 · see citing works
Freeman, G. J., Boussiotis, V. A., Anumanthan, A., Bernstein, G. M., Ke, X.-Y., Rennert, P. D., Gray, G. S., Grlbben, J. G., & Nadler, L. M. (1995) · Immunity · doi:10.1016/1074-7613(95)90032-2 · Cited by 561 · see citing works
Self-citationEgen, J. G., & Allison, J. P. (2002) · Immunity · doi:10.1016/s1074-7613(01)00259-x · Cited by 534 · see citing works
Thurner, B., Röder, C., Dieckmann, D., Heuer, M., Kruse, M., Glaser, A., Keikavoussi, P., Kämpgen, E., Bender, A., & Schuler, G. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(98)00208-7 · Cited by 482 · see citing works
PD-1: an inhibitory immunoreceptor involved in peripheral tolerance
Nishimura, H., & Honjo, T. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(01)01888-9 · Cited by 475 · see citing works
Dendritic cells as a tool to induce anergic and regulatory T cells
Jonuleit, H., Schmitt, E., Steinbrink, K., & Enk, A. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(01)01952-4 · Cited by 464 · see citing works
Steinbrink, K., Graulich, E., Kubsch, S., Knop, J., & Enk, A. (2002) · Blood · doi:10.1182/blood.v99.7.2468 · Cited by 448 · see citing works
Regulation of Antigen-Specific CD8 + T Cell Homeostasis by Perforin and Interferon-γ
Badovinac, V. P., Tvinnereim, A., & Harty, J. T. (2000) · Science · doi:10.1126/science.290.5495.1354 · Cited by 438 · see citing works
Coyle, A. J., & Gutierrez-Ramos, J.-C. (2001) · Nature Immunology · doi:10.1038/85251 · Cited by 412 · 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-citationNishimura, H., Agata, Y., Kawasaki, A., Sato, M., Imamura, S., Minato, N., Yagita∥, H., Nakano, T., & Honjo, T. (1996) · International Immunology · doi:10.1093/intimm/8.5.773 · Cited by 261 · see citing works
Structure 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
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
Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells
Caux, C., Massacrier, C., Vanbervliet, B., Barthélémy, C., Liu, Y.-J., & Banchereau, J. (1994) · International Immunology · doi:10.1093/intimm/6.8.1177 · Cited by 192 · see citing works
Nishimura, H., Honjo, T., & Minato, N. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.5.891 · Cited by 192 · see citing works
Verkaik, N. S., Esveldt, R. E., van Heemst, D., Brüggenwirth, H. T., Hoeijmakers, J. H. J., Zdzienicka, M. Z., & van Gent, D. C. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200203)32:3 · Cited by 189 · see citing works
Activation-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
Förtsch, D., Röllinghoff, M., & Stenger, S. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.2.978 · Cited by 147 · see citing works
Bellinghausen, I., Brand, U., Steinbrink, K., et al. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.117177 · Cited by 113 · see citing works
Kuhns, M. S., Epshteyn, V. A., Sobel, R. A., & Allison, J. P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220423597 · Cited by 67 · see citing works
Functional Effects of TNF and Lymphotoxin α1β2 on FDC-like Cells
Husson, H., Lugli, S. M., Ghia, P., et al. (2000) · Cellular Immunology · doi:10.1006/cimm.2000.1688 · Cited by 50 · see citing works
Dorfman, D. M., & Shahsafaei, A. (1997) · PubMed · Cited by 44 · see citing works
Self-citationThe Leukocyte Semaphorin CD100 Is Expressed in Most T-Cell, but Few B-Cell, Non-Hodgkin's Lymphomas
Dorfman, D. M., Shahsafaei, A., Nadler, L. M., & Freeman, G. J. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65566-6 · Cited by 34 · see citing works
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Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · see citing works
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089 · 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-citationRosenberg, 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
Fehrenbacher, L., Spira, A., Ballinger, M., Kowanetz, M., Vansteenkiste, J., Mazieres, J., Park, K., Smith, D., Artal-Cortes, A., Lewanski, C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00587-0 · Cited by 2,756 · see citing works
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Patel, S. P., & Kurzrock, R. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0983 · Cited by 2,291 · 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
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
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Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608 · see citing works
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Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360 · see citing works
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Okazaki, T., & Honjo, T. (2007) · International Immunology · doi:10.1093/intimm/dxm057 · Cited by 1,310 · see citing works
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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
Thompson, 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
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
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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
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
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Zhu, Y., Yang, J., Xu, D., Gao, X.-M., Zhang, Z., Hsu, J. L., Li, C.-W., Lim, S.-O., Sheng, Y.-Y., Zhang, Y., et al. (2019) · Gut · doi:10.1136/gutjnl-2019-318419 · Cited by 419 · see citing works
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Nakamoto, N., Cho, H., Shaked, A., Olthoff, K., Valiga, M. E., Kaminski, M., Gostick, E., Price, D. A., Freeman, G. J., Wherry, E. J., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000313 · Cited by 380 · see citing works
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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
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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
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Ge, W., Ma, X., Li, X., Wang, Y., Li, C., Meng, H., Liu, X., Yu, Z., You, S., & Qiu, L. (2009) · Leukemia Research · doi:10.1016/j.leukres.2009.01.007 · Cited by 44 · see citing works
- Authors
- Brown, J. A., Dorfman, D. M., Ma, F.-R., Sullivan, E. L., Munoz, O., Wood, C. R., Greenfield, E. A., & Freeman, G. J.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School , Boston, MA 02115
- Wyeth Research , Cambridge, MA 02140
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02-01
- Volume
- 170
- Issue
- 3
- Pages
- 1257-1266
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2154610258
- Cited by
- 968
- References
- 41
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 34 · 2023: 52 · 2022: 32 · 2021: 50 · 2020: 65 · 2019: 46 · 2018: 74 · 2017: 55 · 2016: 60 · 2015: 47 · 2014: 35 · 2013: 38 · 2012: 35
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ai041584-05)
- National Cancer Institute (CA 84500, R01CA084500)
- National Institute of Allergy and Infectious Diseases (AI 39671, AI 41584, P01AI039671)
- 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, PD-L2, PD-1, dendritic cells, T cell activation, T cell proliferation, cytokine production, interferon-gamma, IL-10, immune checkpoint blockade, immature dendritic cells, antigen-presenting cells, peripheral tolerance, tumor immunosuppression
- MeSH terms
- Animals, Antigens, Surface, Binding, Competitive, Blood Proteins, Breast Neoplasms, Cell Membrane, Cells, Cultured, Dendritic Cells, Female, Humans, Immunoglobulin Fab Fragments, Ligands, Lymphocyte Activation, Membrane Glycoproteins, Monocytes, Organ Specificity, Peptides, Proteins, Tumor Cells, Cultured, CD4-Positive T-Lymphocytes, Antigens, CD, Cytokines, Apoptosis, B7-1 Antigen, Intercellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins, Mice, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Programmed Cell Death 1 Ligand 2 Protein
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