Role of the PD-1 pathway in the immune response
Open accessAbstract
Understanding immunoregulatory mechanisms is essential for the development of novel interventions to improve long-term allograft survival. Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, have emerged as critical inhibitory signaling pathways that regulate T cell response and maintain peripheral tolerance. PD-1 signaling inhibits alloreactive T cell activation, and can promote induced regulatory T cell development. Furthermore, the upregulation of PD-L1 on nonhematopoietic cells of the allograft may actively participate in the inhibition of immune responses and provide tissue-specific protection. In murine transplant models, this pathway has been shown to be critical for the induction and maintenance of graft tolerance. In this review, we discuss the current knowledge of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential in transplantation.
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T cell proliferation and function can be enhanced by blocking signalling through inhibitory receptors such as PD-1.
“T cell proliferation and function can also be enhanced by blocking signalling through the inhibitory receptors such as PD-1 [77].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [77]
PD-1/PD-L1 therapy has been reported to impair regulatory T cells in the renal allograft.
“and this is an important strategic point because the use of PD-1/PD-L1 therapy has been reported to impair Treg cells in the renal allograft.173”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [173]
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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 · cited 2× · see citing works
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Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in Utero
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“These T cells develop in the setting of chronic antigenic stimulation (17) and progressively lose effector functions, such as cytokine production and proliferation, leading to a significant deficit in viral clearance (123).”
BackgroundInteractions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal
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“PD-1 signaling has also been implicated in reversal of the “stop signal” that is mediated by TCR signaling (39).”
BackgroundIn Vivo Instruction of Suppressor Commitment in Naive T Cells
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TGF-β Suppresses Tumor Progression in Colon Cancer by Inhibition of IL-6 trans-Signaling
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“However, as discussed earlier in this review, the precise role of the PD-1 pathway in regulating T cell-dependent antibody responses is still unclear (42,43).”
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“In light of the increased awareness of donor-specific alloantibodies as contributors to chronic rejection, interest in TFH in alloimmune responses has expanded.”
BackgroundInfluentialRegulation of PD‐1, PD‐L1, and PD‐L2 expression during normal and autoimmune responses
Liang, S. C., Latchman, Y. E., Buhlmann, J. E., Tomczak, M. F., Horwitz, B. H., Freeman, G. J., & Sharpe, A. H. (2003) · European Journal of Immunology · doi:10.1002/eji.200324228 · Cited by 635 · cited 1× · see citing works
“In addition, it can be upregulated on nonhematopoietic cells, including vascular endothelial cells, epithelial cells, muscle cells, hepatocytes, placental cells and pancreatic islet cells (19,20).”
BackgroundSelf-citationLatchman, Y. E., Liang, S. C., Wu, Y., Chernova, T., Sobel, R. A., Klemm, M., Kuchroo, V. K., Freeman, G. J., & Sharpe, A. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307252101 · Cited by 631 · cited 8× · see citing works
“PD-L1 engagement of its receptors (PD-1, and possibly B7–1) on naı̈ve T cells leads to iTreg development, at least in part, by inhibiting mTOR/Akt signaling, as shown by experiments using microbeads coated with anti-CD3, anti-CD28 and PD-L1 fusion protein as artificial APCs (77).”
BackgroundResultInfluentialSelf-citationPD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells
Loke, P., & Allison, J. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0931259100 · Cited by 630 · cited 1× · see citing works
“IL-4 and GM CSF are the strongest known stimuli for inducing PD-L2 expression (5,12,19,23,24).”
BackgroundFollicular B helper T cells in antibody responses and autoimmunity
Vinuesa, C. G., Tangye, S. G., Moser, B., & Mackay, C. R. (2005) · Nature reviews. Immunology · doi:10.1038/nri1714 · Cited by 624 · cited 2× · see citing works
“Among T cells, TFH have emerged as key supporters of the B cell response (40).”
BackgroundResting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4
Probst, H. C., McCoy, K. D., Okazaki, T., Honjo, T., & van den Broek, M. F. (2005) · Nature Immunology · doi:10.1038/ni1165 · Cited by 554 · cited 1× · see citing works
“PD-1 deficiency on self antigen-specific T cells increases CD8 T cell responses to antigen-bearing resting DCs, and abrogates CD8 T cell tolerance to peripheral self-antigen expression in vivo (30,31,61).”
BackgroundCutting Edge: IL-2 Is Essential for TGF-β-Mediated Induction of Foxp3+ T Regulatory Cells
Davidson, T. S., DiPaolo, R. J., Andersson, J., & Shevach, E. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4022 · Cited by 520 · see citing works
Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes
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“Regulatory T cells Regulatory T cell populations are critical for the maintenance of peripheral tolerance, are potent inhibitors of many immune responses and play an important role in the prevention of graft rejection (64,65).”
BackgroundKinter, 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 · cited 1× · see citing works
“The common c -chain cytokines (IL-2, IL-7, IL-15 and IL-21), TLRs and interferons also can potentiate PD-1 expression on T cells (10).”
BackgroundSalama, A. D., Chitnis, T., Imitola, J., Ansari, M. J., Akiba, H., Tushima, F., Azuma, M., Yagita∥, H., Sayegh, M. H., & Khoury, S. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022119 · Cited by 501 · see citing works
Endothelial expression of PD‐L1 and PD‐L2 down‐regulates CD8+ T cell activation and cytolysis
Rodig, N., Ryan, T., Allen, J. A., Pang, H. B., Grabie, N., Chernova, T., Greenfield, E. A., Liang, S. C., Sharpe, A. H., Lichtman, A. H., et al. (2003) · European Journal of Immunology · doi:10.1002/eji.200324270 · Cited by 494 · cited 2× · see citing works
“In the setting of IFN-c and/or allostimulation, the endothelium is known to upregulate PD-L1 (19,32,116).”
BackgroundSelf-citationSaid, E. A., Dupuy, F. P., Trautmann, L., Zhang, Y., Shi, Y., Far, M. E., Hill, B. J., Noto, A., Ancuța, P., Peretz, Y., et al. (2010) · Nature Medicine · doi:10.1038/nm.2106 · Cited by 474 · see citing works
The Inhibitory Receptor PD-1 Regulates IgA Selection and Bacterial Composition in the Gut
Kawamoto, S., Tran, T. H., Maruya, M., Suzuki, K., Doi, Y., Tsutsui, Y., Kato, L. M., & Fagarasan, S. (2012) · Science · doi:10.1126/science.1217718 · Cited by 451 · cited 1× · see citing works
“PD-1 deficiency can lead to generation of increased numbers of TFH cells with aberrant phenotypes that lead to dysregulated selection of B cells and antibody diversity in germinal centers (44).”
BackgroundThe PDL1-PD1 Axis Converts Human T H 1 Cells into Regulatory T Cells
Amarnath, S., Mangus, C. W., Wang, J. C. M., Wei, F., He, A., Kapoor, V., Foley, J., Massey, P. R., Felizardo, T. C., Riley, J. L., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003130 · Cited by 449 · cited 2× · see citing works
“showed that PD-L1:PD-1 signaling was critical for the conversion of human Th1 cells into Tregs in vivo, preventing the development of xGVHD (81).”
BackgroundA critical role for the programmed death ligand 1 in fetomaternal tolerance
Guleria, I., Khosroshahi, A., Ansari, M. J., Habicht, A., Azuma, M., Yagita∥, H., Noelle, R. J., Coyle, A. J., Mellor, A. L., Khoury, S. J., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050019 · Cited by 439 · cited 1× · see citing works
“Interestingly, PD-L1 blockade or deficiency in B6 females mated with male allogeneic CBA mice results in decreased allogeneic fetal survival rates (113).”
BackgroundEstablishment of NOD- Pdcd1 -/- mice as an efficient animal model of type I diabetes
Wang, J., Yoshida, T., Nakaki, F., Hiai, H., Okazaki, T., & Honjo, T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505497102 · Cited by 436 · cited 1× · see citing works
“However, susceptibility to autoimmune disease is exacerbated in PD-1−/− mice on an autoimmune-prone background (52,53).”
BackgroundNFATc1 Regulates PD-1 Expression upon T Cell Activation
Oestreich, K. J., Yoon, H., Ahmed, R., & Boss, J. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.7.4832 · Cited by 416 · cited 1× · see citing works
“Expression of PD-1 is in part mediated by the recruitment of the nuclear factor of activated T cells c1 (NFATc1) to the nucleus (11).”
BackgroundReinvigorating exhausted HIV-specific T cells via PD-1–PD-1 ligand blockade
Freeman, G. J., Wherry, E. J., Ahmed, R., & Sharpe, A. H. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061800 · Cited by 400 · cited 1× · see citing works
“PD1 is upregulated after TCR or BCR engagement on naı̈ve lymphocytes and persistent antigen stimulation maintains high PD-1 expression (9).”
BackgroundSelf-citationWang, L., Pino‐Lagos, K., de Vries, V. C., Guleria, I., Sayegh, M. H., & Noelle, R. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710441105 · Cited by 390 · cited 1× · see citing works
“PDL1−/− DCs were shown to be defective at supporting the TGFb-induced conversion of naı̈ve T cells to Tregs in vitro, and conversion and maintenance of iTreg function in vivo was also dependent on PD-L1 (79).”
BackgroundB7-H1 Determines Accumulation and Deletion of Intrahepatic CD8+ T Lymphocytes
Dong, H., Zhu, G., Tamada, K., Flies, D. B., van Deursen, J. M. A., & Chen, L. (2004) · Immunity · doi:10.1016/s1074-7613(04)00050-0 · Cited by 370 · see citing works
Deenick, E. K., Chan, A., Ma, C. S., Gatto, D., Schwartzberg, P. L., Brink, R. A., & Tangye, S. G. (2010) · Immunity · doi:10.1016/j.immuni.2010.07.015 · Cited by 344 · cited 1× · see citing works
“TFH cells provide B cell help necessary for the generation of an effective antibody-mediated response (40) and express high amounts of PD-1 (CD44+CXCR5highPD-1high) (104).”
Strauss, L., Whiteside, T. L., Knights, A. J., Bergmann, C., Knuth, A. K., & Zippelius, A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.1.320 · Cited by 335 · see citing works
B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance
Park, J., Omiya, R., Matsumura, Y., Sakoda, Y., Kuramasu, A., Augustine, M. M., Yao, S., Tsushima, F., Narazaki, H., Anand, S., et al. (2010) · Blood · doi:10.1182/blood-2010-01-265975 · Cited by 331 · cited 1× · see citing works
“A similar predominant direction of signaling was observed in a model of tolerance, in which OVA-reactive OT-I T cells undergo activation in response to injection of high-dose OVA257–264 peptide (107).”
BackgroundBlazar, B. R., Carreno, B. M., Panoskaltsis‐Mortari, A., Carter, L., Iwai, Y., Yagita∥, H., Nishimura, H., & Taylor, P. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.3.1272 · Cited by 330 · cited 6× · see citing works
“The accelerated GVHD was dependent on IFN-c , and additional blockade of CTLA-4 further hastened the disease, supporting a nonredundant role of CTLA-4 and PD-1 in GVHD (105).”
BackgroundInfluentialEngagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease
Paust, S., Lu, L., McCarty, N., & Cantor, H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403342101 · Cited by 328 · cited 1× · see citing works
“A function for B7–1 on T cells has been suggested previously (108).”
BackgroundInsulin-induced remission in new-onset NOD mice is maintained by the PD-1–PD-L1 pathway
Fife, B. T., Guleria, I., Bupp, M. G., Eagar, T. N., Tang, Q., Bour-Jordan, H., Yagita∥, H., Azuma, M., Sayegh, M. H., & Bluestone, J. A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061577 · Cited by 325 · cited 1× · see citing works
“For example, the PD-1 pathway is a critical mediator of tolerance induced by administration of antigen-coupled fixed splenocytes, which can reverse diabetes in NOD mice (60).”
BackgroundFranceschini, D., Paroli, M., Francavilla, V., Videtta, M., Morrone, S., Labbadia, G., Cerino, A., Mondelli, M. U., & Barnaba, V. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36604 · Cited by 316 · cited 2× · see citing works
“Antibody blockade studies suggest that this pathway inhibits expansion of established Tregs, as well as effector T cells (89,90).”
BackgroundB cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells
Lee, S. K., Rigby, R. J., Zotos, D., Tsai, L. M., Kawamoto, S., Marshall, J. L., Ramiscal, R. R., Chan, T. D., Gatto, D., Brink, R. A., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20102065 · Cited by 312 · cited 1× · see citing works
“TFH express high levels of PD-1 (15,41), and PD-L1 and PD-L2 are upregulated on germinal center B cells (42).”
BackgroundTGFβ signalling in control of T-cell-mediated self-reactivity
Rubtsov, Y. P., & Rudensky, A. Y. (2007) · Nature reviews. Immunology · doi:10.1038/nri2095 · Cited by 311 · see citing works
Zhou, Q., Munger, M. E., Highfill, S., Tolar, J., Weigel, B., Riddle, M. J., Sharpe, A., Vallera, D., Azuma, M., Levine, B., et al. (2010) · Blood · doi:10.1182/blood-2010-03-275446 · Cited by 307 · cited 1× · see citing works
“Furthermore, in a model of acute myeloid leukemia, adoptively transferred AML-reactive cytotoxic T cells were more effective at eradicating the tumor after PD-L1 blockade (106).”
BackgroundSelf-citationEndothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8 + T-Cell–Mediated Injury in the Heart
Grabie, N., Gotsman, I., DaCosta, R., Pang, H. B., Stavrakis, G., Butte, M. J., Keir, M. E., Freeman, G. J., Sharpe, A. H., & Lichtman, A. H. (2007) · Circulation · doi:10.1161/circulationaha.107.709360 · Cited by 291 · cited 1× · see citing works
“Indeed, nonhematopoietic expression of PD-L1 contributes to prevention of diabetes in the NOD mouse model (36) and regulates self-reactive CD8+ T cell responses in other models of self-tolerance (30,115).”
BackgroundSelf-citationPD-1 Protects against Inflammation and Myocyte Damage in T Cell-Mediated Myocarditis
Tarrio, M. L., Grabie, N., Bu, D.-X., Sharpe, A. H., & Lichtman, A. H. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200389 · Cited by 288 · cited 1× · see citing works
“PD-1 deficiency on self antigen-specific T cells increases CD8 T cell responses to antigen-bearing resting DCs, and abrogates CD8 T cell tolerance to peripheral self-antigen expression in vivo (30,31,61).”
BackgroundSelf-citationWang, S., Bajorath, J., Flies, D. B., Dong, H., Honjo, T., & Chen, L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021752 · Cited by 288 · cited 1× · see citing works
“There are data to suggest that PD-L2 may have another receptor, the identity of which is still unknown (26).”
BackgroundSchreiner, B., Mitsdoerffer, M., Kieseier, B. C., Chen, L., Hartung, H.-P., Weller, M., & Wiendl, H. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.06.013 · Cited by 276 · cited 1× · see citing works
“IL-4 and GM CSF are the strongest known stimuli for inducing PD-L2 expression (5,12,19,23,24).”
BackgroundExpression 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
Selenko-Gebauer, N., Majdic, O., Szekeres, A., Höfler, G., Guthann, E., Korthäuer, U., Zlabinger, G. J., Steinberger, P., Pickl, W. F., Stockinger, H. S. J., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.7.3637 · Cited by 261 · cited 1× · see citing works
“For example, PD-L1 expression is high in tolerogenic subsets of DCs, Tregs and mesenchymal stem cells (32,100,101), whereas the expression of PD-L2 is mostly restricted to professional APCs.”
BackgroundDuraiswamy, J., Ibegbu, C., Masopust, D., Miller, J. D., Araki, K., Doho, G., Tata, P., Sk, G., Zilliox, M. J., Nakaya, H. I., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001783 · Cited by 246 · see citing works
T‐cell tolerance or function is determined by combinatorial costimulatory signals
Nurieva, R., Thomas, S., Nguyen, T. D., Martín‐Orozco, N., Wang, Y., Murali‐Krishna, K., Yu, X., & Dong, C. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601146 · Cited by 245 · cited 2× · see citing works
“However, a strong positive signaling through CD28 and/or IL-2 receptor can overcome PD-1 inhibitory effects on T cell proliferation, differentiation and survival (5,18,37,38).”
BackgroundPD-1 Regulates Self-Reactive CD8+ T Cell Responses to Antigen in Lymph Nodes and Tissues
Keir, M. E., Freeman, G. J., & Sharpe, A. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5064 · Cited by 243 · cited 2× · see citing works
“Indeed, nonhematopoietic expression of PD-L1 contributes to prevention of diabetes in the NOD mouse model (36) and regulates self-reactive CD8+ T cell responses in other models of self-tolerance (30,115).”
BackgroundSelf-citationProgrammed Death-1 Targeting Can Promote Allograft Survival
Özkaynak, E., Wang, L., Goodearl, A. D. J., McDonald, K., Qin, S., O’Keefe, T. L., Duong, T., Smith, T., Gutierrez-Ramos, J.-C., Rottman, J. B., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.11.6546 · Cited by 242 · see citing works
Maternal Acceptance of the Fetus: True Human Tolerance
Guleria, I., & Sayegh, M. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3345 · Cited by 235 · cited 2× · see citing works
“PD-L1 is highly expressed on Tregs and in trophoblasts lining the decidua layer of the placenta (111).”
BackgroundDejean, A. S., Beisner, D. R., Ch’en, I. L., Kerdiles, Y. M., Babour, A., Arden, K. C., Castrillón, D. H., DePinho, R. A., & Hedrick, S. Μ. (2009) · Nature Immunology · doi:10.1038/ni.1729 · Cited by 235 · cited 2× · see citing works
“However, American Journal of Transplantation 2012; 12: 2575–2587 2581 there are some studies indicating that B7–1 may signal into DCs and lead to the upregulation of IDO (109,110).”
BackgroundSo, T., & Croft, M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.3.1427 · Cited by 211 · see citing works
Tanaka, K., Albin, M. J., Yuan, X., Yamaura, K., Habicht, A., Murayama, T., Grimm, M. R., Waaga, A. M., Ueno, T., Padera, R. F., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5204 · Cited by 207 · see citing works
PD-1 on dendritic cells impedes innate immunity against bacterial infection
Yao, S., Wang, S., Zhu, Y., Luo, L., Zhu, G., Flies, S. J., Xu, H., Ruff, W. E., Broadwater, M., Choi, I.-H., et al. (2009) · Blood · doi:10.1182/blood-2009-02-203141 · Cited by 205 · cited 1× · see citing works
“Recently described roles for PD-1 expression on DCs and monocytes highlight the possibility that PD-1 signaling may also occur independently of T cell or B cell antigen receptor signaling, possibly by impinging on other receptor signaling pathways (45,46).”
BackgroundCostimulatory pathways in transplantation: challenges and new developments
Li, X. C., Rothstein, D. M., & Sayegh, M. H. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00781.x · Cited by 197 · cited 1× · see citing works
“Some costimulatory interactions potentiate the activation and proliferation of naı̈ve T cells, while others inhibit T cell activation and promote regulation (1,2).”
BackgroundNishimura, H., Honjo, T., & Minato, N. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.5.891 · Cited by 192 · see citing works
Lucas, J. A., Weinmann‐Menke, J., Rabacal, W., Schöen, F. J., Sharpe, A. H., & Kelley, V. R. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.4.2513 · Cited by 191 · see citing works
Self-citationKuipers, H., Muskens, F., Willart, M. A. M., Hijdra, D., van Assema, F., Coyle, A. J., Hoogsteden, H. C., & Lambrecht, B. N. (2006) · European Journal of Immunology · doi:10.1002/eji.200635978 · Cited by 191 · cited 1× · see citing works
“Data supporting PD-L1 and/or PDL2 signaling are primarily based on experiments using soluble PD-1 reagents that engage PD-L1/2 and lead to upregulation of IL-10 production and reduction in DC function (4,47).”
BackgroundZhong, X., Tumang, J. R., Gao, W., Bai, C., & Rothstein, T. L. (2007) · European Journal of Immunology · doi:10.1002/eji.200737461 · Cited by 190 · cited 1× · see citing works
“PD-L2 is upregulated on DCs, macrophages, bone marrow-derived mast cells and on a subset of peritoneal B1 B cells as well as on germinal center B cells (21).”
BackgroundVerkaik, 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
Role of the Programmed Death-1 Pathway in Regulation of Alloimmune Responses In Vivo
Sandner, S. E., Clarkson, M. R., Salama, A. D., Fueyo, A. S., Domenig, C. M., Habicht, A., Najafian, N., Yagita∥, H., Azuma, M., Turka, L. A., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3408 · Cited by 186 · cited 4× · see citing works
“While PD-1 upregulation on naı̈ve T cells peaks at 48 h after anti-CD3 or anti-CD3/anti-CD28 stimulation in vitro (12), PD-1 on allogeneic CD4+ T cells progressively increases over time following skin transplantation in vivo, reaching the highest levels on day 10 posttransplant (13).”
BackgroundMethodInfluentialThe Link between the PDL1 Costimulatory Pathway and Th17 in Fetomaternal Tolerance
D’Addio, F., Riella, L. V., Mfarrej, B. G., Chabtini, L., Adams, L. T., Yeung, M. Y., Yagita∥, H., Azuma, M., Sayegh, M. H., & Guleria, I. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002031 · Cited by 172 · see citing works
Self-citationRegulation 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 159 · cited 1× · see citing works
“PD-L2 is required for oral tolerance, as shown by failure of oral tolerance in PD-L2−/− mice (62).”
BackgroundGao, W., Demirci, G., Strom, T. B., & Li, X. C. (2003) · Transplantation · doi:10.1097/01.tp.0000085010.39567.fb · Cited by 158 · cited 2× · see citing works
“Similarly, PD-L1-Ig prevented islet allograft rejection and facilitated tolerance induction when combined with anti-CD154 or suboptimal doses of rapamycin (118).”
BackgroundKrupnick, A. S., Gelman, A. E., Barchet, W., Richardson, S., Kreisel, F. H. C., Turka, L. A., Colonna, M., Patterson, G. A., & Kreisel, D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6265 · Cited by 157 · see citing works
Ito, T., Ueno, T., Clarkson, M. R., Yuan, X., Jurewicz, M. M., Yagita∥, H., Azuma, M., Sharpe, A. H., Auchincloss, H., Sayegh, M. H., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.11.6648 · Cited by 153 · see citing works
Self-citationKeir, M. E., Latchman, Y. E., Freeman, G. J., & Sharpe, A. H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.11.7372 · Cited by 151 · see citing works
Self-citationExpression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells.
Eppihimer, M. J., Gunn, J., Freeman, G. J., Greenfield, E. A., Chernova, T., Erickson, J., & Leonard, J. P. (2002) · PubMed · doi:10.1038/sj/mn/7800123 · Cited by 149 · see citing works
CD4 + CD25 + Regulatory Cells from Human Peripheral Blood Express Very High Levels of CD25 Ex Vivo
Baecher‐Allan, C., Brown, J. A., Freeman, G. J., & Hafler, D. A. (2003) · Novartis Foundation symposium · doi:10.1002/0470871628.ch6 · Cited by 136 · cited 1× · see citing works
“Last, certain subsets of T cells express high levels of PD-1, including CD4+Foxp3+ regulatory T cells (Tregs) (14), T follicular helper cells (TFH) (15), memory T cells (16) and “exhausted” CD8 cells (17).”
BackgroundHams, E., McCarron, M. J., Amu, S., Yagita∥, H., Azuma, M., Chen, L., & Fallon, P. G. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003161 · Cited by 136 · cited 2× · see citing works
“However, as discussed earlier in this review, the precise role of the PD-1 pathway in regulating T cell-dependent antibody responses is still unclear (42,43).”
BackgroundResultYang, J., Riella, L. V., Chock, S., Liu, T., Zhao, X., Yuan, X., Paterson, A. M., Watanabe, T., Vanguri, V. K., Yagita∥, H., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100056 · Cited by 134 · cited 5× · see citing works
“Our studies revealed a significantly greater effect of a blocking anti-PD-L1 mAb as compared to a blocking anti-PD-1 mAb in alloimmunity (98,99).”
BackgroundMethodResultInfluentialSelf-citationAbe, M., Wang, Z., Creus, A. D., & Thomson, A. W. (2005) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.00954.x · Cited by 125 · cited 1× · see citing works
“For example, PD-L1 expression is high in tolerogenic subsets of DCs, Tregs and mesenchymal stem cells (32,100,101), whereas the expression of PD-L2 is mostly restricted to professional APCs.”
BackgroundPD‐1/B7‐H1 Interaction Contribute to the Spontaneous Acceptance of Mouse Liver Allograft
Morita, M., Fujino, M., Jiang, G., Kitazawa, Y., Xie, L., Azuma, M., Yagita∥, H., Nagao, S., Sugioka, A., Kurosawa, Y., et al. (2009) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2009.02859.x · Cited by 120 · cited 4× · see citing works
“lymphocytes and increased levels of inflammatory cytokines (92).”
BackgroundInfluentialThe effect of immunosuppressive drug rapamycin on regulatory CD4+CD25+Foxp3+T cells in mice.
Qu, Y., Zhang, B., Zhao, L., Liu, G.-W., Ma, H.-X., Rao, E. Y., Zeng, C., & Zhao, Y. (2007) · Transplant Immunology · doi:10.1016/j.trim.2007.01.002 · Cited by 118 · see citing works
PD-L2 is expressed on activated human T cells and regulates their function
Messal, N., Serriari, N., Pastor, S., Nunès, J. A., & Olive, D. (2011) · Molecular Immunology · doi:10.1016/j.molimm.2011.06.436 · Cited by 116 · cited 1× · see citing works
“PD-L2 is also expressed on human, but not mouse, vascular endothelial cells and T cells (6,22).”
BackgroundTGF-β1 modulates Foxp3 expression and regulatory activity in distinct CD4+ T cell subsets
Pyzik, M., & Piccirillo, C. A. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.1006644 · Cited by 115 · see citing works
Blank, C. U., Brown, I., Marks, R., Nishimura, H., Honjo, T., & Gajewski, T. F. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.9.4574 · Cited by 111 · cited 1× · see citing works
“Two studies using the alloreactive 2C TCR transgenic model showed increased negative selection in the absence of PD-1 (53,58), while analysis of HY-specific CD4 and CD8 TCR transgenic mice revealed no role for PD-1 in negative selection (59).”
BackgroundYang, J., Popoola, J., Khandwala, S., Vadivel, N., Vanguri, V. K., Yuan, X., Dada, S., Guleria, I., Tian, C., Ansari, M. J., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.741025 · Cited by 96 · cited 3× · see citing works
“In less allogeneic models, such as the MHC class II mismatched model (bm12 into B6), blockade of PD-L1 also precipitated rejection, whereas PD-1 and PD-L2 blockade had no effect on graft survival (96,99).”
BackgroundSelf-citationRenal tubular PD-L1 (CD274) suppresses alloreactive human T-cell responses
Starke, A., Lindenmeyer, M. T., Segerer, S., Neusser, M. A., Rüsi, B., SCHMID, D. M., Cohen, C. D., Wuthrich, R. P., Fehr, T. H., & Waeckerle‐Men, Y. (2010) · Kidney International · doi:10.1038/ki.2010.97 · Cited by 89 · cited 1× · see citing works
“Furthermore, in human kidney transplantation, tubular epithelial cells were found to upregulate PD-L1 during acute allograft rejection and PDL1 on human tubular epithelial cell cultures was capable of inhibiting proliferation and cytokine production of CD4+ and CD8+ T cells (117).”
BackgroundProgrammed cell death 1 (PD‐1) and its ligand PD‐L1 are required for allograft tolerance
Wang, L., Han, R., & Hancock, W. W. (2007) · European Journal of Immunology · doi:10.1002/eji.200737583 · Cited by 80 · cited 2× · see citing works
“Furthermore, blockade or elimination of PD-L1 also abrogates other tolerogenic strategies, such as antiCD154 mAb combined with donor-specific transfusion (95).”
BackgroundChadha, R., Heidt, S., Jones, N. D., & Wood, K. J. (2011) · Transplantation · doi:10.1097/tp.0b013e3182126eeb · Cited by 75 · cited 1× · see citing works
“Mouse models of liver transplantation (103) are very interesting to investigate, since the majority of liver grafts are”
BackgroundRiella, L. V., Watanabe, T., Sage, P. T., Yang, J., Yeung, M. Y., Azzi, J. R., Vanguri, V. K., Chandraker, A. K., Sharpe, A. H., Sayegh, M. H., et al. (2011) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2011.03451.x · Cited by 67 · cited 7× · see citing works
“BALB/c PD-L1 chimera → B6 PD-L1 chimeric donor Graft PD-L1 expression on both hematopoietic and nonhematopoietic cells are essential for tolerance ↑CD8 eff mem ↑IFN-c , GrB (32)”
BackgroundMethodInfluentialSelf-citationLin, S.-J., Peacock, C. D., Bahl, K., & Welsh, R. M. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062150 · Cited by 62 · cited 2× · see citing works
“In a lymphopenic environment, a subpopulation of PD-1high T cells develop that have skewed TCR repertoires and appear to be preapoptotic (63).”
BackgroundYi, T., Li, X.-F., Yao, S., Wang, L., Chen, Y.-H., Zhao, D., Johnston, H. F., Young, J. S., Liu, H., Todorov, I., et al. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1002939 · Cited by 57 · cited 2× · see citing works
“Antibody blockade studies suggest that this pathway inhibits expansion of established Tregs, as well as effector T cells (89,90).”
BackgroundThangavelu, G., Parkman, J., Ewen, C., Uwiera, R. R. E., Baldwin, T. A., & Anderson, C. C. (2011) · Journal of Autoimmunity · doi:10.1016/j.jaut.2011.02.009 · Cited by 56 · cited 2× · see citing works
“Two studies using the alloreactive 2C TCR transgenic model showed increased negative selection in the absence of PD-1 (53,58), while analysis of HY-specific CD4 and CD8 TCR transgenic mice revealed no role for PD-1 in negative selection (59).”
BackgroundKoehn, B. H., Ford, M. L., Ferrer, I. R., Borom, K., Gangappa, S., Kirk, A. D., & Larsen, C. P. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.8.5313 · Cited by 53 · cited 11× · see citing works
“The role of PD-1 in Treg conversion was partially mediated by the activation of intracellular SHP1/2 and consequent reduction of STAT1 phosphorylation, thereby abrogating IFN-c -mediated maintenance of T-bet and favoring Foxp3 expression (81).”
BackgroundMethodInfluentialGene Transfer of Programmed Death Ligand-1.Ig Prolongs Cardiac Allograft Survival
Dudler, J., Li, J., Pagnotta, M., Pascual, M. A., von Segesser, . K., & Vassalli, G. (2006) · Transplantation · doi:10.1097/01.tp.0000250757.69384.79 · Cited by 47 · cited 2× · see citing works
“F344→ Lewis (rat model) Overexpression of PD-L1 on donor heart via adenovirus ± cyclosporine Slight delay in rejection in combination with cyclosporine ↓CD4 graft infiltration (119)”
MethodWang, C., Li, Y., Proctor, T. M., Vandenbark, A. A., & Offner, H. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22181 · Cited by 43 · see citing works
A Novel Alloantigen-Specific CD8+PD1+ Regulatory T Cell Induced by ICOS-B7h Blockade In Vivo
Izawa, A., Yamaura, K., Albin, M. J., Jurewicz, M. M., Tanaka, K., Clarkson, M. R., Ueno, T., Habicht, A., Freeman, G. J., Yagita∥, H., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.2.786 · Cited by 42 · cited 1× · see citing works
“In addition, a subpopulation of regulatory allo-specific CD8+ T cells expressing PD-1, which is induced by ICOS: B7h blockade, was found to be important for immune regulation (91).”
BackgroundWang, R., Carper, K., Malone, F. R., Latchman, Y. E., Perkins, J. D., Fu, Y., Reyes, J. D., & Li, W. (2008) · Transplantation · doi:10.1097/tp.0b013e3181861932 · Cited by 37 · cited 7× · see citing works
“PD-L1 engagement of its receptors (PD-1, and possibly B7–1) on naı̈ve T cells leads to iTreg development, at least in part, by inhibiting mTOR/Akt signaling, as shown by experiments using microbeads coated with anti-CD3, anti-CD28 and PD-L1 fusion protein as artificial APCs (77).”
InfluentialMcDermott, D. F., Drake, C. G., Sznol, M., Sosman, J. A., Smith, D. C., Powderly, J. D., Feltquate, D., Kollia, G. D., Gupta, A. K., & Wigginton, J. M. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.7_suppl.331 · Cited by 29 · see citing works
Memory T cells and their exhaustive differentiation in allograft tolerance and rejection
Valujskikh, A., & Li, X. C. (2011) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32834ee443 · Cited by 23 · cited 1× · see citing works
“Whether “exhausted” T cells develop in the setting of alloimmunity is not known, and is a subject for future investigation (124).”
BackgroundPeng, W., Ran, B., Ma, Y., Huang, X., Chang, Q., & Wang, X. (2011) · Cellular Immunology · doi:10.1016/j.cellimm.2011.06.007 · Cited by 15 · cited 2× · see citing works
“While all control rats died prior to 12 days after transplant, PD-L1-DC-treated rats had greater than 60% survival at 3 weeks posttransplant (120).”
Background
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Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,314 · see citing works
Oncology meets immunology: the cancer-immunity cycle.
Chen, D. S., & Mellman, I. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.012 · Cited by 6,929 · see citing works
Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
“PD-1 is an inhibitor receptor, playing a key role in programmed death signaling in order to regulate T- cell mediated responses [32].”
BackgroundStructure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1
Żak, K. M., Kitel, R., Przetocka, S., Golik, P., Guzik, K., Musielak, B., Dömling, A. S. S., Dubin, G., & Holak, T. A. (2015) · Structure · doi:10.1016/j.str.2015.09.010 · Cited by 541 · see citing works
“Thereby, under normal conditions, the PD-1/PD-L1 pathway prevents excessive stimulation and maintains the immune tolerance to self-antigens by negatively regulating the immune response (Riella et al., 2012).”
BackgroundWu, M., Huang, Q., Xie, Y., Wu, X., Ma, H., Zhang, Y., & Xia, Y. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01242-2 · Cited by 471 · see citing works
“Generally, the PD-1/PD-L1 pathway prevents the overstimulation of T cells and maintains immune tolerance to self-antigens, thereby reducing damage to surrounding tissues and preventing autoimmune diseases from developing [37, 38].”
BackgroundStructural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2
Żak, K. M., Grudnik, P., Magiera‐Mularz, K., Dömling, A. S. S., Dubin, G., & Holak, T. A. (2017) · Structure · doi:10.1016/j.str.2017.06.011 · Cited by 386 · see citing works
PD-1 and its ligands are important immune checkpoints in cancer
Dong, Y., Sun, Q., & Zhang, X. (2016) · Oncotarget · doi:10.18632/oncotarget.13895 · Cited by 339 · see citing works
“PD-L2 is expressed mainly on antigenpresenting cells (APCs), including macrophages and myeloid DCs, and non-hematopoietic tissues, such as the lung [62, 63].”
BackgroundSkalniak, Ł., Żak, K. M., Guzik, K., Magiera‐Mularz, K., Musielak, B., Pachota, M., Szelążek, B., Kocik-Krol, J., Grudnik, P., Tomala, M. D., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20050 · Cited by 308 · see citing works
“The inhibitory signal is provided by PD-L1, the ligand of PD1, which is naturally expressed on the antigen-presenting cells (APCs) and in a variety of tissues [8].”
BackgroundNeuroinflammation in Alzheimer’s Disease
Onyango, I. G., Jauregui, G. V., Čarná, M., Bennett, J. P., & Stokin, G. B. (2021) · Biomedicines · doi:10.3390/biomedicines9050524 · Cited by 330 · see citing works
“Together with its widely expressed ligand PD-L1, PD-1 plays an important role in maintaining immune homeostasis and self-tolerance [387,388].”
BackgroundSoluble PD-1 and PD-L1: predictive and prognostic significance in cancer
Zhu, X., & Lang, J. (2017) · Oncotarget · doi:10.18632/oncotarget.18311 · Cited by 301 · see citing works
Senescence of T Lymphocytes: Implications for Enhancing Human Immunity
Akbar, A. N., Henson, S. M., & Lanna, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.09.002 · Cited by 285 · see citing works
“Strikingly, administration of blocking antibodies to CTLA4/PD1 can restore glucose metabolism in mouse TILs contributing to tumour eradication [68].”
BackgroundInfluentialLi, S., Siriwon, N., Zhang, X., Yang, S., Jin, T., He, F., Kim, K. G., Mac, J., Lu, Z., Wang, S. P., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0867 · Cited by 302 · see citing works
“The insert for CAR.aPD1 vector consisted of the following components in frame 50 end to 30 end: a NotI site, the anti-CD19 CAR, a leader sequence derived from human IL2, the anti-PD-1 scFv light chain variable region, a GS linker, the anti–PD-1 scFv heavy chain variable region, the HA-tag sequence, and an EcoRI site.”
BackgroundProbiotics importance and their immunomodulatory properties
Yousefi, B., Eslami, M., Ghasemian, A., Kokhaei, P., Farrokhi, A. S., & Darabi, N. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27559 · Cited by 278 · see citing works
OX40 Agonists and Combination Immunotherapy: Putting the Pedal to the Metal
Linch, S. N., McNamara, M. J., & Redmond, W. L. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00034 · Cited by 238 · see citing works
Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti–PD-L1 Antibodies
Heskamp, S., Hobo, W. A., Molkenboer‐Kuenen, J. D. M., Olive, D., Oyen, W. J. G., Dolstra, H., & Boerman, O. C. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3477 · Cited by 234 · see citing works
“T cells also express coinhibitory molecules that are capable of downregulating the immune response.(1) One major coinhibitory receptor is programmed death 1 (PD-1).”
BackgroundImmunotherapy for advanced hepatocellular carcinoma: a focus on special subgroups
Pinter, M., Scheiner, B., & Peck‐Radosavljevic, M. (2020) · Gut · doi:10.1136/gutjnl-2020-321702 · Cited by 234 · see citing works
Haanen, J., Ernstoff, M. S., Wang, Y., Menzies, A. M., Puzanov, I., Grivas, P., Larkin, J., Peters, S., Thompson, J. A., & Obeid, M. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.03.285 · Cited by 222 · see citing works
Carman, C. V., & Martinelli, R. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00603 · Cited by 208 · see citing works
“…in combination with whole animal genetic knock-out strains (e.g., of the APC coinhibitor molecule PD-L1), essential contributions of nhAPCs have been revealed in promoting tolerance in settings of diabetes (83, 85), atherosclerosis (86), organ transplant (87, 88), myocarditis (89), and EAE (90).”
BackgroundDonnelly, D. J., Smith, R. A., Morin, P. E., Lipovšek, D., Gokemeijer, J., Cohen, D., Lafont, V., Tran, T., Cole, E. L., Wright, M. C., et al. (2017) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.199596 · Cited by 194 · see citing works
“Lane (1): total binding of 18F-BMS-986192, lane (2) 0.”
BackgroundMethodResultInfluentialCA-170 – A Potent Small-Molecule PD-L1 Inhibitor or Not?
Musielak, B., Kocik-Krol, J., Skalniak, Ł., Magiera‐Mularz, K., Sala, D., Czub, M., Stec, M., Siedlar, M., Holak, T. A., & Plewka, J. (2019) · Molecules · doi:10.3390/molecules24152804 · Cited by 171 · see citing works
“PD-1 is expressed at the cell surface of activated T and B cells, monocytes, dendritic cells and natural killer (NK) T cells [11,12].”
Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options
Velu, V., Shetty, R. D., Larsson, M., & Shankar, E. M. (2015) · Retrovirology · doi:10.1186/s12977-015-0144-x · Cited by 153 · see citing works
“PD-L1 is upregulated on macrophages and APCs in response to LPS and GM-CSF treatment, and on T cells and B cells upon TCR and B cell receptor signaling [110].”
Immune Checkpoint Inhibitors in Organ Transplant Patients
Kittai, A. S., Oldham, H., Cetnar, J., & Taylor, M. (2017) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000180 · Cited by 151 · see citing works
Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance
Tung, K. S. K., Harakal, J., Qiao, H., Rival, C. M., Li, J. C. H., Paul, A., Wheeler, K. M., Pramoonjago, P., Grafer, C. M., Sun, W., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89927 · Cited by 144 · see citing works
Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies
Harris, C. T., & Cohen, S. (2024) · BioDrugs · doi:10.1007/s40259-023-00641-2 · Cited by 140 · see citing works
“However, they also carry risks, such as the potential for general immunosuppression and increased susceptibility to infections and malignancies [147].”
BackgroundLiver Allograft Failure After Nivolumab Treatment—A Case Report With Systematic Literature Research
Gassmann, D., Weiler, S., Mertens, J. C., Reiner, C. S., Vrugt, B., Nägeli, M., Mangana, J., Müllhaupt, B., Jenni, F., & Misselwitz, B. (2018) · Transplantation Direct · doi:10.1097/txd.0000000000000814 · Cited by 139 · see citing works
d’Izarny-Gargas, T., Dürrbach, A., & Zaidan, M. (2020) · American Journal of Transplantation · doi:10.1111/ajt.15811 · Cited by 142 · see citing works
“0) Progression-free survival (weeks)—median (95% CI) Overall (n = 67) 19 (14-36) Melanoma (n = 32) 17 (13-∞) Treated with ipilimumab (n = 12) 20.”
Photodynamic therapy combined with immunotherapy: Recent advances and future research directions
Warszyńska, M., Repetowski, P., & Dąbrowski, J. M. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215350 · Cited by 138 · see citing works
Preserved renal-allograft function and the PD-1 pathway inhibitor nivolumab
Barnett, R., Barta, V. S., & Jhaveri, K. D. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1614298 · Cited by 136 · see citing works
Organization of the skin immune system and compartmentalized immune responses in infectious diseases
Quaresma, J. A. S. (2019) · Clinical Microbiology Reviews · doi:10.1128/cmr.00034-18 · Cited by 149 · see citing works
Kumar, S., Chatterjee, M., Ghosh, P., Ganguly, K. K., Basu, M., & Ghosh, M. K. (2022) · Genes & Diseases · doi:10.1016/j.gendis.2022.07.024 · Cited by 132 · see citing works
“Recently, it was found that PD-L1 was also expressed on several cancer cells including BCa.(8,9) PI3K-AKT-PKCq signaling axis in T cell regulation”
BackgroundExosomal PD‐L1 functions as an immunosuppressant to promote wound healing
Su, D., Tsai, H., Xu, Z., Yan, F., Wu, Y., Xiao, Y., Liu, X., Wu, Y., Parvanian, S., Zhu, W., et al. (2019) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2019.1709262 · Cited by 129 · see citing works
“The PD-1/PD-L1 immune checkpoint pathway prevents excessive tissue destruction during inflammatory states [20].”
BackgroundAnti-PD-1/PD-L1 therapy for infectious diseases: learning from the cancer paradigm
Rao, M., Valentini, D., Dodoo, E., Zumla, A. I., & Maeurer, M. J. (2017) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2017.01.028 · Cited by 122 · see citing works
TGFβ-dependent expression of PD-1 and PD-L1 controls CD8+ T cell anergy in transplant tolerance
Baas, M. C., Besançon, A., Goncalves, T., Valette, F., Yagita∥, H., Sawitzki, B., Volk, H., Waeckel-Énée, E., Rocha, B., Chatenoud, L., et al. (2016) · eLife · doi:10.7554/elife.08133 · Cited by 116 · see citing works
“DOI: 10.7554/eLife.08133 13 of 19 the establishment of tolerance (Barber et al., 2006; Haspot et al., 2008; Ito et al., 2005; Lucas et al., 2011; Riella et al., 2012).”
BackgroundInfluentialCommensal microbiota regulates T cell fate decision in the gut
Furusawa, Y., Obata, Y., & Hase, K. (2014) · Seminars in Immunopathology · doi:10.1007/s00281-014-0455-3 · Cited by 114 · see citing works
“, CD80 and CD86) expressed on DCs [20–22].”
BackgroundSoluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways
Liu, C., Jiang, J., Gao, L., Wang, X., Hu, X., Wu, M., Wu, J. H., Xu, T., Shi, Q., & Zhang, X. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0859-z · Cited by 113 · see citing works
“Programmed cell death 1 (PD-1; also called CD279), which is inducibly expressed on CD4 T cells, CD8 T cells, natural killer T cells, B cells, and activated monocytes, is a type I membrane protein that delivers inhibitory signals to T cells upon binding of its ligands PD-L1 or PD-L2 [10–13].”
BackgroundLiu, S., Chen, S., Yuan, W., Wang, H., Chen, K., Li, D., & Li, D. (2017) · Oncotarget · doi:10.18632/oncotarget.21914 · Cited by 112 · see citing works
“PD-1, also known as CD279, is the receptor of PD-L1; it is expressed by activated NK cells, dendritic cells, as well as T cells and B cells [7].”
BackgroundThe importance of the PD-1/PD-L1 pathway at the maternal-fetal interface
Meggyes, M., Mikó, É., Szigeti, B., Farkas, N., & Szereday, L. (2019) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-019-2218-6 · Cited by 110 · see citing works
Emerging trends in the immunotherapy of pancreatic cancer
Banerjee, K., Sushil Kumar, K., Ross, K. A., Gautam, S. K., Poelaert, B. J., Nasser, M. W., Aithal, A., Bhatia, R., Wannemuehler, M. J., Narasimhan, B., et al. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.12.012 · Cited by 106 · see citing works
“PD-1 on T-cells interacts with two B7 family ligands, PD-L1 (CD274) and PD-L2 (CD273) expressed on tumor cells that leads to T-cell anergy or death and thus leading to tumor survival [37].”
BackgroundCardiorenal complications of immune checkpoint inhibitors
Sury, K., Perazella, M. A., & Shirali, A. C. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0035-1 · Cited by 106 · see citing works
Liu, C., Seeram, N. P., & Ma, H. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01946-4 · Cited by 104 · see citing works
“By contrast, PD-1 expression maintains a high level in chronically stimulated antigen-specific T cells, which leads to their functional exhaustion in response to stimuli [52].”
The PD-1/B7-H1 Pathway Modulates the Natural Killer Cells versus Mouse Glioma Stem Cells
Huang, B. Y., Zhan, Y. P., Zong, W. J., Yu, C. J., Li, J., Qu, Y. M., & Han, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134715 · Cited by 102 · see citing works
Immune Landscape of Thyroid Cancers: New Insights
Menicali, E., Guzzetti, M., Morelli, S., Moretti, S., & Puxeddu, E. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.637826 · Cited by 98 · see citing works
“tissue damage in chronic infections and prevent autoimmunity (89).”
BackgroundMechanisms of Mixed Chimerism-Based Transplant Tolerance
Zuber, J., & Sykes, M. (2017) · Trends in Immunology · doi:10.1016/j.it.2017.07.008 · Cited by 94 · see citing works
“Furthermore, the PD1 ligand PDL-1, whose role is increasingly evident in transplant immunology [105], is strongly inducible by tubular epithelial cells on alloimmune attack [106].”
Immunotherapy and transplantation for hepatocellular carcinoma
Tabrizian, P., Abdelrahim, M., & Schwartz, M. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.01.011 · Cited by 95 · see citing works
The Role of Immune Checkpoint Inhibitors in Cancer Therapy
Basudan, A. (2022) · Clinics and Practice · doi:10.3390/clinpract13010003 · Cited by 94 · see citing works
“PD-1 is also a member of the immunoglobulin superfamily and plays a key coinhibitory role in the signaling of programmed cell death in response to the T-cell-mediated process [37].”
BackgroundChoi, J., Cooper, M. L., Staser, K. W., Ashami, K., Vij, K. R., Wang, B., Marsala, L. I., Niswonger, J., Ritchey, J., Alahmari, B., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0123-z · Cited by 90 · see citing works
Immunotherapy via PD-L1–presenting biomaterials leads to long-term islet graft survival
Coronel, M. M., Martin, K. E., Hunckler, M. D., Barber, G., O’Neill, E. B., Medina, J. D., Opri, E., McClain, C. A., Batra, L., Weaver, J. D., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba5573 · Cited by 89 · see citing works
Revolutionizing Cancer Treatment: Recent Advances in Immunotherapy
Ghemrawi, R., Abuamer, L., Kremesh, S., Hussien, G., Ahmed, R., Mousa, W. K., Khoder, G., & Khair, M. (2024) · Biomedicines · doi:10.3390/biomedicines12092158 · Cited by 92 · see citing works
Both PD-1 Ligands Protect the Kidney from Ischemia Reperfusion Injury
Jaworska, K., Ratajczak, J., Huang, L., Whalen, K., Yang, M., Stevens, B. K., & Kinsey, G. R. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400497 · Cited by 88 · see citing works
“pression is limited primarily to APCs (29, 30).”
BackgroundInfluentialShi, X., Mancham, S., Hansen, B. E., de Knegt, R. J., de Jonge, J., van der Laan, L. J. W., Rivadeneira, F., Metselaar, H. J., & Kwekkeboom, J. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.034 · Cited by 86 · see citing works
Use of the PD-1 Pathway Inhibitor Nivolumab in a Renal Transplant Patient With Malignancy
Boils, C. L., Aljadir, D., & Cantafio, A. W. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13786 · Cited by 82 · see citing works
“However, given the temporal association with this patient’s rejection and knowing the protective role of PD-1 signaling for allograft tolerance (2,3), we propose that chemotherapeutic agents that block the PD-1 signaling pathway be studied further and that multidisciplinary collaboration occur in this patient populati…”
BackgroundNeoadjuvant Interferons: Critical for Effective PD-1–Based Immunotherapy in TNBC
Brockwell, N. K., Owen, K. L., Zanker, D. J., Spurling, A., Rautela, J., Duivenvoorden, H. M., Baschuk, N., Caramia, F., Loi, S., Darcy, P. K., et al. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0150 · Cited by 83 · see citing works
“As IFN-based immune activation can cause secondary dampening of immunity via PD-L1 induction (28),wehypothesized that PD-1blockadewould result indurable responses from immune activating therapies.”
BackgroundThe Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy
Singh, A., Ham, J., Po, J. W., Niles, N., Roberts, T. L., & Lee, C. S. (2021) · Cells · doi:10.3390/cells10051082 · Cited by 81 · see citing works
Follicular helper T cells: new insights into mechanisms of autoimmune diseases.
Zhang, X., Ing, S., Fraser, A., Chen, M., Khan, O., Zakem, J., Davis, W., & Quinet, R. (2013) · Europe PMC (PubMed Central) · Cited by 80 · see citing works
Antitumor activity of nivolumab on hemodialysis after renal allograft rejection
Ong, M., Ibrahim, A. M., Bourassa‐Blanchette, S., Canil, C., Fairhead, T., & Knoll, G. A. (2016) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0171-8 · Cited by 81 · see citing works
“…function; 3) complicated medical management of addressing organ failure (e.g. hemodialysis) and co-morbidities that led to organ failure (e.g. diabetes); 4) evolving treatment landscape with multiple immune checkpoints that differ in mechanism and tolerability (i.e. CTLA-4 versus PD-1) [7, 10, 15].”
BackgroundImmunomodulatory Bonds of the Partnership between Dendritic Cells and T Cells
Bourque, J., & Hawiger, D. (2018) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2018026790 · Cited by 78 · see citing works
Wu, L., Lin, W., Liao, Q., Wang, H., Lin, C., Tang, L., Lian, W., Chen, Z., Li, K., Xu, L., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108327 · Cited by 79 · see citing works
Oncolytic virus and PD-1/PD-L1 blockade combination therapy
Chen, C., Hutzen, B. J., Wedekind, M. F., & Cripe, T. P. (2018) · Oncolytic Virotherapy · doi:10.2147/ov.s145532 · Cited by 78 · see citing works
“20 PD-1 is a type I trans-membrane receptor of the immunoglobulin superfamily.”
Au, K. P., & Chok, K. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i45.5081 · Cited by 79 · see citing works
Waliany, S., Lee, D. C., Witteles, R. M., Neal, J. W., Nguyen, P. K. P., Davis, M. M., Salem, J., Wu, S. M., Moslehi, J. J., & Zhu, H. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023451 · Cited by 75 · see citing works
Nguyen, L. S., Ortuno, S., Lebrun‐Vignes, B., Johnson, D. B., Moslehi, J. J., Hertig, A., & Salem, J. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.01.038 · Cited by 81 · see citing works
Huang, X., Chen, Y., Chung, C., Yuan, Z., Monaghan, S. F., Wang, F., & Ayala, A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1302252 · Cited by 73 · see citing works
“Also, the impact of B7-H1 gene deficiency may include actions mediated through immune:nonimmune cells (27).”
BackgroundAutoreactive B cells in SLE, villains or innocent bystanders?
Hamilton, J. A., Hsu, H., & Mountz, J. D. (2019) · Immunological Reviews · doi:10.1111/imr.12815 · Cited by 73 · see citing works
Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients
Manohar, S., Thongprayoon, C., Cheungpasitporn, W., Markovic, S. N., & Herrmann, S. M. (2019) · Kidney International Reports · doi:10.1016/j.ekir.2019.11.015 · Cited by 74 · see citing works
“CD4 regulatory T cells, T follicular helper cells, memory cells, and exhausted CD8 cells typically have high levels of PD-1 expression.(49) The inhibitors that are T-cell extrinsic are present on the tissue (e.”
BackgroundFaghfuri, E., Faramarzi, M. A., Nikfar, S., & Abdollahi, M. R. (2015) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.2015.1074862 · Cited by 72 · see citing works
“Mechanism of action (PD-1/PD-L1 pathway & anti-PD-1 agents) The PD-1 receptor is a 50–55 kDa type I transmembrane glycoprotein of the Ig superfamily on tumor infiltrating lymphocytes (TIL) and T-regulatory cells (Treg) [17].”
BackgroundSpary, L. K., Salimu, J., Webber, J. P., Clayton, A., Mason, M. D., & Tabi, Z. (2014) · OncoImmunology · doi:10.4161/21624011.2014.955331 · Cited by 71 · see citing works
“The DCs arising from stromal regulation have an immunosuppressive phenotype, including increased expression of PD-L1.”
BackgroundInfluentialArruda, L. C. M., de Azevedo, J. T. C., de Oliveira, G. L. V., Scortegagna, G. T., Rodrigues, E. S., Palma, P. V. B., Brum, D. G., Guerreiro, C. T., Marques, V. D., Barreira, A. A., et al. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.06.005 · Cited by 70 · see citing works
“The interaction between PD-1 and its ligands (PDL-1 and PDL-2) lead to transduction of inhibitory intracellular signals, resulting in suppression of T-cell activation and effector responses [30,32].”
Chang, H., Jung, W., Kim, A., Kim, H. K., Kim, W. B., Kim, J. H., & Kim, B. (2017) · Apmis · doi:10.1111/apm.12703 · Cited by 70 · see citing works
“PD-1/PDL1 pathway involves inhibition of T-cell function via dephosphorylation of signaling intermediates resulting in decreased T-cell proliferation and cytokine production including IFN-c (6).”
BackgroundBeyond PD-L1 Markers for Lung Cancer Immunotherapy
Wojas‐Krawczyk, K., Kalinka‐Warzocha, E., Grenda, A., Krawczyk, P. A., & Milanowski, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081915 · Cited by 70 · see citing works
“The lymphocyte inhibitory signal is transmitted through PD-1 as a result of its interaction with the ligand—the PD-L1 molecule [21,23,24].”
BackgroundQiu, H. X., Wu, H., Chan, V. S. F., Lau, C.-S., & Lu, Q. (2017) · Autoimmunity · doi:10.1080/08916934.2017.1284821 · Cited by 67 · see citing works
Immune Checkpoint Inhibitors in Urothelial Bladder Cancer: State of the Art and Future Perspectives
Roviello, G., Catalano, M., Santi, R., Palmieri, V. E., Vannini, G., Galli, I. C., Buttitta, E., Villari, D., Rossi, V., & Nesi, G. (2021) · Cancers · doi:10.3390/cancers13174411 · Cited by 64 · see citing works
“PD-L1 is expressed on immune cells, such as T cells, B cells, dendritic cells (DCs) and macrophages [20,21], while PD-L2 is expressed mainly on antigen-presenting cells (APCs), including macrophages and myeloid DCs [22,23].”
BackgroundSun, H., Sun, C., & Xiao, W. (2013) · Cytokine · doi:10.1016/j.cyto.2013.09.016 · Cited by 64 · see citing works
“Programmed death-1 (PD-1), also termed as CD279, is a distant member of CD28 family, with a single immunoglobulin superfamily domain and a cytoplasmic domain containing two motifs: an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immnoreceptor tyrosine-based switch motif (ITSM) [13,14].”
BackgroundLim, H., Chun, J.-H., Jin, X., Kim, J., Yoon, J., & No, K. T. (2019) · Scientific Reports · doi:10.1038/s41598-019-53216-z · Cited by 61 · see citing works
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“When PD-1 is blocked, this process no longer occurs, and T cells can proliferate and injure kidney tissue.(79)”
BackgroundSafety of an anti-PD-1 immune checkpoint inhibitor in a liver transplant recipient
Biondani, P., Martin, E. D., & Samuel, D. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx548 · Cited by 60 · see citing works
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PD-L1 and immune escape: insights from melanoma and other lineage-unrelated malignancies
Frydenlund, N., & Mahalingam, M. (2017) · Human Pathology · doi:10.1016/j.humpath.2017.06.012 · Cited by 58 · see citing works
Troiano, G., Caponio, V. C. A., Zhurakivska, K., Arena, C., Pannone, G., Mascitti, M., Santarelli, A., & Muzio, L. L. (2018) · Cell Proliferation · doi:10.1111/cpr.12537 · Cited by 57 · see citing works
Regulatory T cell-based therapies for autoimmunity.
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Understanding the checkpoint blockade in lung cancer immunotherapy
Bello, M. G. D., Alama, A., Coco, S., Vanni, I., & Grossi, F. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.05.016 · Cited by 55 · see citing works
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Immune checkpoint inhibitors: a narrative review of considerations for the anaesthesiologist
Lewis, A., Chaft, J. E., Girotra, M., & Fischer, G. W. (2020) · British Journal of Anaesthesia · doi:10.1016/j.bja.2019.11.034 · Cited by 56 · see citing works
“PD-1 (CD279) receptor is expressed broadly on peripheral CD4þ and CD8þ T cells, B cells, and myeloid cells.(14,16) The ligands PD-L1 (CD274) and PD-L2 (CD273) are not exclusively expressed on antigen-presenting cells and tumour”
BackgroundLi, X.-S., Li, J., Li, H., & Jiang, T. (2020) · Bioscience Reports · doi:10.1042/bsr20200459 · Cited by 56 · see citing works
Passariello, M., D’Alise, A. M., Esposito, A., Vetrei, C., Froechlich, G., Scarselli, E., Nicosia, A., & Lorenzo, C. D. (2019) · Scientific Reports · doi:10.1038/s41598-019-49485-3 · Cited by 55 · see citing works
Kidney organoids: a pioneering model for kidney diseases
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Self-citationRetinal Pigment Epithelial Cells are a Potential Reservoir for Ebola Virus in the Human Eye
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“Both PD-L1 and PD-L2 regulate the function of T cells including the CD8 þ subset, 60 and increased expression would be expected to reduce an adaptive immune response that might otherwise target EBOV in the eye.”
Immune checkpoints and cancer development: Therapeutic implications and future directions
Mehdizadeh, S., Bayatipoor, H., Pashangzadeh, S., Jafarpour, R., Shojaei, Z., & Motallebnezhad, M. (2021) · Pathology - Research and Practice · doi:10.1016/j.prp.2021.153485 · Cited by 55 · see citing works
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PD-L1/PD-1 axis as a potent therapeutic target in breast cancer
Bastaki, S., Irandoust, M., Ahmadi, A., Hojjat‐Farsangi, M., Ambrose, P., Hallaj, S., Edalati, M., Ghalamfarsa, G., Azizi, G., Yousefi, M., et al. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117437 · Cited by 50 · see citing works
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“The circulating levels of inhibitory PD-L1 and other costimulatory signals determine the extent of T-cell activation and the threshold between tolerance and autoimmunity [14].”
BackgroundTolerance induction using nanoparticles bearing HY peptides in bone marrow transplantation
Hlavaty, K. A., McCarthy, D. P., Saito, E., Yap, W. T., Miller, S. D., & Shea, L. D. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.10.041 · Cited by 50 · see citing works
Ortiz, J. A., Maroun‐Eid, C., Martín‐Quirós, A., Toledano, V., Cubillos‐Zapata, C., Gómez‐Campelo, P., Varela-Serrano, A., Casas-Martín, J., Llanos-González, E., Álvarez, E., et al. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix279 · Cited by 48 · see citing works
CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection
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Humoral autoimmunity: A failure of regulatory T cells?
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“PD-1 has 2 ligands, programmed death-ligand 1 (PD-L1) and PD-L2 that bind to PD-1 and induce downregulation and apoptosis in most PD-1(1) leukocytes.(7) PD-L1 and PD-L2 are expressed by HRS cells as a result of upregulation of 9p24.”
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“The PD-1/ PD-L1 pathway plays a critical role in regulating autoreactive lymphocytes and providing balance between protective immunity and tolerance [25, 36].”
BackgroundThe NOD Mouse Beyond Autoimmune Diabetes
Aubin, A., Lombard‐Vadnais, F., Collin, R., Aliesky, H. A., McLachlan, S. M., & Lesage, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.874769 · Cited by 47 · see citing works
PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications
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“Two different type I transmembrane proteins, structurally related to the B7 family, bind to the PD-1 receptor, namely the PD-L1 (B7-H1 or CD274) and the PD-L2 (B7-DC or CD273) [54,55].”
BackgroundInfluentialShwetank, Frost, E. L., Mockus, T. E., Ren, H. M., Toprak, M., Lauver, M. D., Netherby, C. S., Jin, G., Cosby, J., Evavold, B. D., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00783 · Cited by 47 · see citing works
“PD-L1 is expressed on a variety of cell types while the expression of PD-L2 is limited to antigen presenting cells (5) (6) (7) .”
BackgroundZhang, L., Yu, Z., Tu, Q., Xue, X., Zhu, X., & Zhao, K. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200128105459 · Cited by 46 · see citing works
- Authors
- Riella, L. V., Paterson, A. M., Sharpe, A. H., & Chandraker, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Riella, L.V.
- Venue
- American Journal of Transplantation
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 12
- Issue
- 10
- Pages
- 2575-2587
- ISSN
- 1600-6135 (ISSN-L)
- PMC
- PMC3784243
- OpenAlex
- W2144601357
- Cited by
- 444
- References
- 132
- Citations by year
- 2026: 25 · 2025: 25 · 2024: 39 · 2023: 35 · 2022: 33 · 2021: 40 · 2020: 38 · 2019: 36 · 2018: 42 · 2017: 50 · 2016: 25 · 2015: 22 · 2014: 21 · 2013: 13
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Transplantation (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institute of Allergy and Infectious Diseases (R01AI051559, P01 AI 56299, R01 AI-51559, P01AI056299)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- PD-1 pathway, PD-L1, PD-L2, allograft tolerance, immune regulation, regulatory T cells, peripheral tolerance, graft survival
- MeSH terms
- Graft Survival, Humans, Immune Tolerance, Lymphocyte Activation, Signal Transduction, Organ Transplantation, T-Lymphocytes, Regulatory, Programmed Cell Death 1 Receptor
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