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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 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]
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“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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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
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 15,320
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
Regulatory T Cells and Immune Tolerance
Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008) · Cell · doi:10.1016/j.cell.2008.05.009 · Cited by 5,475 · cited 1×
“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).”
BackgroundPD-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 · cited 2×
“PD-1 is inducibly expressed by T cells and B cells after activation (7) as well as natural killer T (NKT) cells, NK cells, activated monocytes and some subsets of dendritic cells (DCs) [reviewed in (8)].”
BackgroundSelf-citationFreeman, 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 · cited 2×
“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 Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in Gastric Cancer
Zhang, L., Xu, J., Zhang, X., Zhang, Y., Wang, L., Huang, X., & Xu, Z. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479442 · Cited by 4,090
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · cited 2×
“Therefore, additional markers such as CD223 (LAG-3), CD244 (2B4) and TIM-3 might be required to correctly identify this subset of T cells (121).”
BackgroundBennett, C. L., Christie, J., Ramsdell, F., Brunkow, M., Ferguson, P., Whitesell, L., Kelly, T., Saulsbury, F., Chance, P., & Ochs, H. (2001) · Nature Genetics · doi:10.1038/83713 · Cited by 3,576 · cited 1×
“CD4+Foxp3+ Tregs, the most widely studied suppressive T cell population, are critical for peripheral tolerance as illustrated by the fatal autoimmune condition of scurfy mice and the human immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), both caused by mutations in the foxp3 gene (66,67…”
Background
Research works printed but not linked: 1
- McDermott, 2011, A phase I study to evaluate safety and antitumor activity of biweekly BMS-936558 in patients with RCC and other advanced refractory malignancies, J Clin Oncol, 29
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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 15,320
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
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
“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 561
“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 484
“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 393
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 350
“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 315
“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
“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 308
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
“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 309
“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 292
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 243
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 238
“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 238
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
Carman, C. V., & Martinelli, R. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00603 · Cited by 214
“…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 196
“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 173
“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
“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
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
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 148
“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
d’Izarny-Gargas, T., Dürrbach, A., & Zaidan, M. (2020) · American Journal of Transplantation · doi:10.1111/ajt.15811 · Cited by 144
“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 142
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
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
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 135
“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 128
“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 125
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
“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 121
“, 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
“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 116
“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
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 107
“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
Liu, C., Seeram, N. P., & Ma, H. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01946-4 · Cited by 105
“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
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
“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 98
“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
The Role of Immune Checkpoint Inhibitors in Cancer Therapy
Basudan, A. (2022) · Clinics and Practice · doi:10.3390/clinpract13010003 · Cited by 99
“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 89
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
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 97
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
“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
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
“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
“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 84
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
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
“…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 79
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
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 79
“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
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 77
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
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
“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 74
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
“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
“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 74
“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 71
“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
“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 71
“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 69
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 66
“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 65
“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
Mangan, B. L., McAlister, R. K., Balko, J. M., Johnson, D. B., Moslehi, J. J., Gibson, A., & Phillips, E. J. (2020) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14433 · Cited by 62
“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
Almawash, S. (2025) · Cancers · doi:10.3390/cancers17050880 · Cited by 69
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 62
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
Regulatory T cell-based therapies for autoimmunity.
Arellano, B., Graber, D. J., & Sentman, C. L. (2016) · PubMed · Cited by 56
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
Li, Y., Shen, M., Xu, L. J., Yang, X., Tsai, Y., Keng, P. C., Chen, Y., & Lee, S. O. (2017) · Scientific Reports · doi:10.1038/s41598-017-08483-z · Cited by 56
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 60
“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
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
Kidney organoids: a pioneering model for kidney diseases
Tekgüç, M., van Gaal, R. C., Uzel, S. G. M., Gupta, N. R., Riella, L. V., Lewis, J. A., & Morizane, R. (2022) · Translational research · doi:10.1016/j.trsl.2022.06.012 · Cited by 55
Self-citationRetinal Pigment Epithelial Cells are a Potential Reservoir for Ebola Virus in the Human Eye
Smith, J. R., Todd, S., Ashander, L. M., Charitou, T., Ma, Y., Yeh, S., Crozier, I., Michael, M., Appukuttan, B., Williams, K. A., et al. (2017) · Translational Vision Science & Technology · doi:10.1167/tvst.6.4.12 · Cited by 54
“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
Varki, V., Ioffe, O. B., Bentzen, S. M., Heath, J., Cellini, A., Feliciano, J. L., & Zandberg, D. P. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2138-8 · Cited by 52
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 51
Pizarro, C., García‐Díaz, D. F., Ethel Codner, D., Salas‐Pérez, F., Carrasco, E., & Pérez‐Bravo, F. (2014) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2552 · Cited by 51
“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
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
CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection
Khairnar, V., Duhan, V., Patil, A., Zhou, F., Bhat, H., Thöns, C., Sharma, P., Adomati, T., Friendrich, S.-K., Bezgovsek, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04832-2 · Cited by 49
Humoral autoimmunity: A failure of regulatory T cells?
Dhaeze, T., Stinissen, P., Liston, A., & Hellings, N. (2015) · Autoimmunity Reviews · doi:10.1016/j.autrev.2015.04.006 · Cited by 47
Hollander, P., Kamper, P., Smedby, K. E. E., Enblad, G., Ludvigsen, M., Mortensen, J. B., Amini, R., Hamilton-Dutoit, S. J., d’Amore, F., Molin, D., et al. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017006346 · Cited by 47
“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.”
BackgroundWalankiewicz, M., Grywalska, E., Polak, G., Korona‐Głowniak, I., Witt, E., Surdacka, A., Kotarski, J., & Roliński, J. (2018) · Mediators of Inflammation · doi:10.1155/2018/7041342 · Cited by 48
“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 51
PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications
Ulisse, S., Tuccilli, C., Sorrenti, S., Antonelli, A., Fallahi, P., D’Armiento, E., Catania, A., Tartaglia, F., Amabile, M. I., Giacomelli, L., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061405 · Cited by 46
“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
“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 51
Metadata
- 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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