PD-1 signaling in primary T cells

Riley, James L.

doi:10.1111/j.1600-065x.2009.00767.x

Cited by 781Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyPhagocytosis and Immune Regulation

PD-1 signaling in primary T cells

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Riley, James L.·2009·Immunological Reviews

DOI 10.1111/j.1600-065x.2009.00767.xPMC PMC3424066

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Abstract

Summary: Programmed death‐1 (PD‐1) is a cell surface molecule that regulates the adaptive immune response. Engagement of PD‐1 by its ligands PD‐L1 or PD‐L2 transduces a signal that inhibits T‐cell proliferation, cytokine production, and cytolytic function. While a great deal is known concerning the biologic roles PD‐1 plays in regulating the primary immune response and in T‐cell exhaustion, comparatively little is known regarding how PD‐1 ligation alters signaling pathways. PD‐1 ligation is known to inhibit membrane‐proximal T‐cell signaling events, while ligation of the related inhibitory molecule cytotoxic T‐lymphocyte antigen‐4 appears to target more downstream signaling pathways. A major obstacle to an in‐depth understanding of PD‐1 signaling is the lack of physiologic models in which to study signal transduction. This review focuses on: (i) signaling pathways altered by PD‐1 ligation, (ii) factors recruited upon PD‐1 phosphorylation, and (iii) exploring the hypothesis that PD‐1 ligation induces distinct signals during various stages of immune‐cell differentiation. Lastly, we describe models to dissect the function of the PD‐1 cytoplasmic tail using primary cells in the absence of agonist antibodies.

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Recruitment of SHP-1 and/or SHP-2 to the ITSM in the PD-1 cytoplasmic tail inhibits signaling, particularly PI3K/AKT activation downstream of the T-cell receptor, causing T cell dysfunction.
“it is suggested that recruitment of SH2-domain containing protein tyrosine phosphatases (SHP-1 and/or SHP-2) to the immunoreceptor tyrosine-based switch motif (ITSM) within the PD-1 cytoplasmic tail inhibits signaling events, particularly PI3K/AKT activation, downstream signals of the T-cell receptor [34], and in turn results in T cell dysfunction.”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [34]

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Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378 · see citing works
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 3,960 · see citing works
Induced expression of PD‐1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259 · see citing works
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955 · see citing works
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680 · see citing works
B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion
Dong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496 · see citing works
The B7 family revisited
Greenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318 · see citing works
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103 · see citing works
Siglecs and their roles in the immune system
Crocker, P. R., Paulson, J. C., & Varki, A. P. (2007) · Nature reviews. Immunology · doi:10.1038/nri2056 · Cited by 2,032 · see citing works
CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms
Parry, R. V., Chemnitz, J. M., Frauwirth, K. A., Lanfranco, A. R., Braunstein, I., Kobayashi, S. V., Linsley, P. S., Thompson, C. B., & Riley, J. L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9543-9553.2005 · Cited by 1,931 · see citing works
Self-citation
Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell Responses
Butte, M. J., Keir, M. E., Phamduy, T. B., Sharpe, A. H., & Freeman, G. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.016 · Cited by 1,733 · see citing works
The B7–CD28 superfamily
Sharpe, A. H., & Freeman, G. J. (2002) · Nature reviews. Immunology · doi:10.1038/nri727 · Cited by 1,719 · see citing works
Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
Trautmann, L., Janbazian, L., Chomont, N., Said, E. A., Gimmig, S., Bessette, B., Boulassel, M.-R., Delwart, E., Sepulveda, H., Balderas, R. S., et al. (2006) · Nature Medicine · doi:10.1038/nm1482 · Cited by 1,565 · see citing works
The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection
Sharpe, A. H., Wherry, E. J., Ahmed, R., & Freeman, G. J. (2007) · Nature Immunology · doi:10.1038/ni1443 · Cited by 1,519 · see citing works
The CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475 · see citing works
Self-citation
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.11.006 · Cited by 1,355 · see citing works
PD-1 and PD-1 ligands: from discovery to clinical application
Okazaki, T., & Honjo, T. (2007) · International Immunology · doi:10.1093/intimm/dxm057 · Cited by 1,310 · see citing works
The ‘Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling
Neel, B. G., Gu, H., & Pao, L. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00091-4 · Cited by 1,249 · see citing works
SHP-1 and SHP-2 Associate with Immunoreceptor Tyrosine-Based Switch Motif of Programmed Death 1 upon Primary Human T Cell Stimulation, but Only Receptor Ligation Prevents T Cell Activation
Chemnitz, J. M., Parry, R. V., Nichols, K. E., June, C. H., & Riley, J. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.2.945 · Cited by 1,246 · see citing works
Self-citation
Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide–based retroviral vector
Szymczak-Workman, A. L., Workman, C. J., Wang, Y., Vignali, K. M., Dilioglou, S., Vanin, E. F., & Vignali, D. A. A. (2004) · Nature Biotechnology · doi:10.1038/nbt957 · Cited by 1,160 · see citing works
Control of peripheral T‐cell tolerance and autoimmunity via the CTLA‐4 and PD‐1 pathways
Fife, B. T., & Bluestone, J. A. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00662.x · Cited by 1,052 · see citing works
CTLA-4: new insights into its biological function and use in tumor immunotherapy
Egen, J. G., Kuhns, M. S., & Allison, J. P. (2002) · Nature Immunology · doi:10.1038/ni0702-611 · Cited by 940 · see citing works
PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection
Petrovas, C., Casazza, J. P., Brenchley, J. M., Price, D. A., Gostick, E., Adams, W. C., Precopio, M. L., Schacker, T., Roederer, M., Douek, D. C., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061496 · Cited by 889 · see citing works
BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1
Watanabe, N., Gavrieli, M., Sedy, J. R., Yang, J., Fallarino, F., Loftin, S. K., Hurchla, M. A., Zimmerman, N., Sim, J., Zang, X., et al. (2003) · Nature Immunology · doi:10.1038/ni944 · Cited by 883 · see citing works
PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine
Okazaki, T., Maeda, A., Nishimura, H., Kurosaki, T., & Honjo, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231486598 · Cited by 849 · see citing works
Fuel feeds function: energy metabolism and the T-cell response
Fox, C. J., Hammerman, P. S., & Thompson, C. B. (2005) · Nature reviews. Immunology · doi:10.1038/nri1710 · Cited by 841 · see citing works
Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor FeγRIIB
Ono, M., Bolland, S. M., Tempst, P., & Ravetch, J. V. (1996) · Nature · doi:10.1038/383263a0 · Cited by 781 · see citing works
The PD-1–PD-L pathway in immunological tolerance
Okazaki, T., & Honjo, T. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.02.001 · Cited by 720 · see citing works
Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src
Nada, S., Okada, M., MacAuley, A., Cooper, J. A., & Nakagawa, H. (1991) · Nature · doi:10.1038/351069a0 · Cited by 622 · see citing works
Jurkat T cells and development of the T-cell receptor signalling paradigm
Abraham, R. T., & Weiss, A. (2004) · Nature reviews. Immunology · doi:10.1038/nri1330 · Cited by 602 · see citing works
Resting 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 · see citing works
Directed evolution of human T-cell receptors with picomolar affinities by phage display
Li, Y., Moysey, R. K., Molloy, P. E., Vuidepot, A., Mahon, T., Baston, E., Dunn, S. M., Liddy, N., Jacob, J. P., Jakobsen, B. K., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1070 · Cited by 442 · see citing works
Establishment 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 · see citing works
PD-1 and its ligands in T-cell immunity
Keir, M. E., Francisco, L. M., & Sharpe, A. H. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.04.012 · Cited by 432 · see citing works
LAIR-1, a Novel Inhibitory Receptor Expressed on Human Mononuclear Leukocytes
Meyaard, L., Adema, G. J., Chang, C., Woollatt, E., Sutherland, G. R., Lanier, L. L., & Phillips, J. H. (1997) · Immunity · doi:10.1016/s1074-7613(00)80530-0 · Cited by 401 · see citing works
Reinvigorating 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 · see citing works
Direct Regulation of ZAP-70 by SHP-1 in T Cell Antigen Receptor Signaling
Plas, D. R., Johnson, R. R., Pingel, J. T., Matthews, R. J., Dalton, M., Roy, G., Chan, A. C., & Thomas, M. L. (1996) · Science · doi:10.1126/science.272.5265.1173 · Cited by 392 · see citing works
Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling.
Rudd, C. E., & Schneider, H. (2003) · Nature Reviews Immunology · doi:10.1038/nri1131 · Cited by 392 · see citing works
Role of SH-PTP2, a Protein-Tyrosine Phosphatase with Src Homology 2 Domains, in Insulin-Stimulated Ras Activation
Noguchi, T., Matozaki, T., Horita, K., Fujioka, Y., & Kasuga, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.10.6674 · Cited by 376 · see citing works
Stable antibody expression at therapeutic levels using the 2A peptide
Fang, J., Qian, J., Yi, S., Harding, T. C., Tu, G. H., VanRoey, M. J., & Jooss, K. U. (2005) · Nature Biotechnology · doi:10.1038/nbt1087 · Cited by 370 · see citing works
Deficiency of PTEN in Jurkat T Cells Causes Constitutive Localization of Itk to the Plasma Membrane and Hyperresponsiveness to CD3 Stimulation
Shan, X., Czar, M. J., Bunnell, S. C., Liu, P., Liu, Y., Schwartzberg, P. L., & Wange, R. L. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.18.6945-6957.2000 · Cited by 341 · see citing works
Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation
Diehn, M., Alizadeh, A. A., Rando, O. J., Liu, C. L., Stankunas, K., Botstein, D., Crabtree, G. R., & Brown, P. O. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092284399 · Cited by 336 · see citing works
Variability and Robustness in T Cell Activation from Regulated Heterogeneity in Protein Levels
Feinerman, O., Veiga, J., Dorfman, J. R., Germain, R. N., & Altan-Bonnet, G. Y. (2008) · Science · doi:10.1126/science.1158013 · Cited by 332 · see citing works
Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signalling
Zhang, J., Somani, A.-K. B., & Siminovitch, K. A. (2000) · Seminars in Immunology · doi:10.1006/smim.2000.0223 · Cited by 320 · see citing works
The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation
Riley, J. L., & June, C. H. (2004) · Blood · doi:10.1182/blood-2004-04-1596 · Cited by 314 · see citing works
Self-citation
Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors
Riley, J. L., Mao, M., Kobayashi, S., Biery, M. C., Burchard, J., Cavet, G., Gregson, B. P., June, C. H., & Linsley, P. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162359999 · Cited by 307 · see citing works
Self-citation
The Tyrosine Phosphatase SHP-2 Is Required for Sustained Activation of Extracellular Signal-Regulated Kinase and Epithelial Morphogenesis Downstream from the Met Receptor Tyrosine Kinase
Maroun, C. R., Naujokas, M. A., Holgado-Madruga, M., Wong, A. J., & Park, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8513-8525.2000 · Cited by 286 · see citing works
Engineering Artificial Antigen-presenting Cells to Express a Diverse Array of Co-stimulatory Molecules
Suhoski, M. M., Golovina, T. N., Aqui, N. A., Tai, V. C., Varela-Rohena, A., Milone, M. C., Carroll, R. G., Riley, J. L., & June, C. H. (2007) · Molecular Therapy · doi:10.1038/mt.sj.6300134 · Cited by 266 · see citing works
Self-citation
Identification of the tyrosine phosphatase PTP1C as a B cell antigen receptor-associated protein involved in the regulation of B cell signaling.
Pani, G., Kozlowski, M., Cambier, J. C., Mills, G. B., & Siminovitch, K. A. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.6.2077 · Cited by 251 · see citing works
Multiple Requirements for SHPTP2 in Epidermal Growth Factor-Mediated Cell Cycle Progression
Bennett, A. M., Hausdorff, S. F., O’Reilly, A. M., Freeman, R. M., & Neel, B. G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.1189 · Cited by 246 · see citing works
Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor
Varela‐Rohena, A., Molloy, P. E., Dunn, S. M., Li, Y., Suhoski, M. M., Carroll, R. G., Milicic, A., Mahon, T., Sutton, D. H., Laugel, B., et al. (2008) · Nature Medicine · doi:10.1038/nm.1779 · Cited by 243 · see citing works
Self-citation
SHP2 and SOCS3 Contribute to Tyr-759-dependent Attenuation of Interleukin-6 Signaling through gp130
Lehmann, U., Schmitz, J., Weissenbach, M., Sobota, R. M., Hörtner, M., Friederichs, K., Behrmann, I., Tsiaris, W., Sasaki, A., Schneider-Mergener, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210552200 · Cited by 236 · see citing works
Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C.
Fry, A. M., Lanier, L. L., & Weiss, A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.1.295 · Cited by 208 · see citing works
Loss of Siglec expression on T lymphocytes during human evolution
Nguyen, D. H., Hurtado-Ziola, N., Gagneux, P., & Varki, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510484103 · Cited by 204 · see citing works
Nonreceptor Protein-Tyrosine Phosphatases in Immune Cell Signaling
Pao, L. I., Badour, K., Siminovitch, K., & Neel, B. G. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115647 · Cited by 200 · see citing works
Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells
Verkaik, N. S., Esveldt, R. E., van Heemst, D., Brüggenwirth, H. T., Hoeijmakers, J. H. J., Zdzienicka, M. Z., & van Gent, D. C. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200203)32:3 · Cited by 189 · see citing works
B and T Lymphocyte Attenuator Exhibits Structural and Expression Polymorphisms and Is Highly Induced in Anergic CD4+ T Cells
Hurchla, M. A., Šedý, J. R., Gavrieli, M., Drake, C. G., Murphy, T. L., & MURPHY, K. M. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3377 · Cited by 181 · see citing works
Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness.
Lorenz, U. M., Ravichandran, K. S., Burakoff, S. J., & Neel, B. G. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9624 · Cited by 171 · see citing works
CD28 and Inducible Costimulatory Protein Src Homology 2 Binding Domains Show Distinct Regulation of Phosphatidylinositol 3-Kinase, Bcl-xL, and IL-2 Expression in Primary Human CD4 T Lymphocytes
Parry, R. V., Rumbley, C. A., Vandenberghe, L. H., June, C. H., & Riley, J. L. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.1.166 · Cited by 169 · see citing works
Self-citation
Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor
Roncagalli, R., Taylor, J. E. R., Zhang, S., Shi, X., Chen, R., Cruz‐Munoz, M., Yin, L., Latour, S., & Veillette, A. (2005) · Nature Immunology · doi:10.1038/ni1242 · Cited by 160 · see citing works
Analysis of the Role of Negative T Cell Costimulatory Pathways in CD4 and CD8 T Cell-Mediated Alloimmune Responses In Vivo
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
Involvement of SH2-containing Phosphotyrosine Phosphatase Syp in Erythropoietin Receptor Signal Transduction Pathways
Tauchi, T., Feng, G., Shen, R., Hoatlin, M. E., Bagby, G. C., Kabat, D., Lu, L., & Broxmeyer, H. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5631 · Cited by 139 · see citing works
CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction.
Blair, P. J., Riley, J. L., Levine, B. L., Lee, K. P., Craighead, N., Francomano, T., Perfetto, S. J., Gray, G. S., Carreno, B. M., & June, C. H. (1998) · PubMed · Cited by 135 · see citing works
Self-citation
Growth Factor Receptor-bound Protein 2 SH2/SH3 Domain Binding to CD28 and Its Role in Co-signaling
Kim, H., Tharayil, M., & Rudd, C. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.1.296 · Cited by 135 · see citing works
Mutation of the SHP-2 Binding Site in Growth Hormone (GH) Receptor Prolongs GH-Promoted Tyrosyl Phosphorylation of GH Receptor, JAK2, and STAT5B
Stofega, M. R., Herrington, J. B., Billestrup, N., & Carter‐Su, C. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.9.0513 · Cited by 134 · see citing works
SHP-1- and Phosphotyrosine-Independent Inhibitory Signaling by a Killer Cell Ig-Like Receptor Cytoplasmic Domain in Human NK Cells
Yusa, S.-I., Catina, T. L., & Campbell, K. S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.10.5047 · Cited by 132 · see citing works
Evidence That SHIP-1 Contributes to Phosphatidylinositol 3,4,5-Trisphosphate Metabolism in T Lymphocytes and Can Regulate Novel Phosphoinositide 3-Kinase Effectors
Freeburn, R. W., Wright, K. L., Burgess, S., Astoul, E., Cantrell, D. A., & Ward, S. G. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5441 · Cited by 121 · see citing works
Ligation of CD28 receptor by B7 induces formation of D‐3 phosphoinositides in T lymphocytes independently of T cell receptor/CD3 activation
Ward, S. G., Westwick, J. K., Hall, N. D., & Sansom, D. M. (1993) · European Journal of Immunology · doi:10.1002/eji.1830231029 · Cited by 120 · see citing works
Cutting Edge: CTLA-4 Ligation Delivers a Unique Signal to Resting Human CD4 T Cells That Inhibits Interleukin-2 Secretion but Allows Bcl-XL Induction
Blair, P. J., Riley, J. L., Levine, B. L., Lee, K. P., Craighead, N., Francomano, T., Perfetto, S. J., Gray, G. S., Carreno, B. M., & June, C. H. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.1.12 · Cited by 118 · see citing works
Self-citation
Siglec-5 (CD170) Can Mediate Inhibitory Signaling in the Absence of Immunoreceptor Tyrosine-based Inhibitory Motif Phosphorylation
Avril, T., Freeman, S. D., Attrill, H. L., Clarke, R. G., & Crocker, P. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502041200 · Cited by 102 · see citing works
A Single Amino Acid Alteration in Cytoplasmic Domain Determines IL-2 Promoter Activation by Ligation of CD28 but Not Inducible Costimulator (ICOS)
Harada, Y., Ohgai, D., Watanabe, R., Okano, K., Koiwai, O., Tanabe, K., Toma, H., Altman, A., & Abe, R. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021305 · Cited by 98 · see citing works
A Cell-Based Artificial Antigen-Presenting Cell Coated with Anti-CD3 and CD28 Antibodies Enables Rapid Expansion and Long-Term Growth of CD4 T Lymphocytes
Thomas, A., Maus, M. V., Shalaby, W. S. W., June, C. H., & Riley, J. L. (2002) · Clinical Immunology · doi:10.1006/clim.2002.5277 · Cited by 96 · see citing works
Self-citation
Lentiviral Vectors Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-Specific Inhibitory Activity
Joseph, A., Zheng, J., Follenzi, A., Dilorenzo, T., Sango, K., Hyman, J., Chen, K., Piechocka-Trocha, A., Brander, C., Hooijberg, E., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01812-07 · Cited by 94 · see citing works
B and T Lymphocyte Attenuator-Mediated Signal Transduction Provides a Potent Inhibitory Signal to Primary Human CD4 T Cells That Can Be Initiated by Multiple Phosphotyrosine Motifs
Chemnitz, J. M., Lanfranco, A. R., Braunstein, I., & Riley, J. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.11.6603 · Cited by 85 · see citing works
Self-citation
Association of Grb-2 and PI3K p85 with phosphotyrosile peptides derived from BTLA
Gavrieli, M., & Murphy, K. M. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.05.036 · Cited by 85 · cited 1× · see citing works
“Furthermore, whether the motifs within the BTLA cytoplasmic tail actually recruit Grb2 or related molecules, or whether they are even important for BTLA function, is unclear (27, 28).”
Background
Investigations into the Regulation and Function of the SH2 Domain-Containing Protein-Tyrosine Phosphatase, SHP-1
Tsui, F. W. L., Martín, A., Wang, J., & Tsui, H. W. (2006) · Immunologic Research · doi:10.1385/ir:35:1:127 · Cited by 83 · see citing works
Phosphoinositide Lipid Phosphatases: Natural Regulators of Phosphoinositide 3-Kinase Signaling in T Lymphocytes
Harris, S. J., Parry, R. V., Westwick, J. K., & Ward, S. G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.r700044200 · Cited by 81 · see citing works
Programmed Death 1 Ligand (PD-L) 1 and PD-L2 Limit Autoimmune Kidney Disease: Distinct Roles
Weinmann‐Menke, J., Lucas, J. A., Zeller, G. C., Keir, M. E., Huang, X. R., Tsuboi, N., Mayadas, T. N., Lan, H. Y., Sharpe, A. H., & Kelley, V. R. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.11.7466 · Cited by 79 · see citing works
Constitutive Association of SHP-1 with Leukocyte-Associated Ig-Like Receptor-1 in Human T Cells
Sathish, J. G., Johnson, K. G., FULLER, K. J., LeRoy, F. G., Meyaard, L., Sims, M., & Matthews, R. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.3.1763 · Cited by 75 · see citing works
Adapter Function of Protein-tyrosine Phosphatase 1D in Insulin Receptor/Insulin Receptor Substrate-1 Interaction
Kharitonenkov, A., Schnekenburger, J., Chen, Z., Knyazev, P. G., Ali, S., Zwick, E., White, M. F., & Ullrich, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.49.29189 · Cited by 75 · see citing works
Grb2 Forms an Inducible Protein Complex with CD28 through a Src Homology 3 Domain-Proline Interaction
Okkenhaug, K., & Rottapel, R. K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.33.21194 · Cited by 73 · see citing works
Leukocyte‐associated Ig‐like receptor‐1 has SH2 domain‐containing phosphatase‐independent function and recruits C‐terminal Src kinase
Verbrugge, A., Rijkers, E. S. K., Ruiter, T. E.-D., & Meyaard, L. (2005) · European Journal of Immunology · doi:10.1002/eji.200535226 · Cited by 68 · see citing works
Systematic identification of immunoreceptor tyrosine-based inhibitory motifs in the human proteome
Staub, E., Rosenthal, A., & Hinzmann, B. (2003) · Cellular Signalling · doi:10.1016/j.cellsig.2003.08.013 · Cited by 64 · see citing works
Grb2 and Gads Exhibit Different Interactions with CD28 and Play Distinct Roles in CD28-Mediated Costimulation
Watanabe, R., Harada, Y., Takeda, K., Takahashi, J., Ohnuki, K., Ogawa, S., Ohgai, D., Kaibara, N., Koiwai, O., Tanabe, K., et al. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.1085 · Cited by 62 · see citing works
GRID: A Novel Grb-2-Related Adapter Protein That Interacts with the Activated T Cell Costimulatory Receptor CD28
Ellis, J. H., Ashman, C., Burden, M. N., Kilpatrick, K. E., Morse, M. A., & Hamblin, P. A. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.11.5805 · Cited by 59 · see citing works
STAT5 Is Essential for Akt/p70S6 Kinase Activity during IL-2-Induced Lymphocyte Proliferation
Lockyer, H. M., Tran, E., & Nelson, B. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5301 · Cited by 58 · see citing works
Turning on the off switch: Regulation of anti-viral T cell responses in the liver by the PD-1/PD-L1 pathway
Grakoui, A., Wherry, E. J., Hanson, H. L., Walker, C. M., & Ahmed, R. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.07.009 · Cited by 50 · see citing works
PD-1 deficiency reveals various tissue-specific autoimmunity by H-2 b and dose-dependent requirement of H-2 g7 for diabetes in NOD mice
Yoshida, T., Jiang, F., Honjo, T., & Okazaki, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710951105 · Cited by 49 · see citing works
Differential contribution of the immunoreceptor tyrosine-based inhibitory motifs of human leukocyte-associated Ig-like receptor-1 to inhibitory function and phosphatase recruitment
Verbrugge, A. (2003) · International Immunology · doi:10.1093/intimm/dxg134 · Cited by 47 · see citing works
Recruitment of C-terminal Src kinase by the leukocyte inhibitory receptor CD85j
Sayós, J., Martínez‐Barriocanal, Á., Kitzig, F., Bellón, T., & López‐Botet, M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.09.097 · Cited by 45 · see citing works
Dendritic Cells in Transplantation and Immune-Based Therapies
Young, J. W., Mérad, M., & Hart, D. N. J. (2007) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2006.10.023 · Cited by 34 · see citing works
Novel strategies to eliminate persistent viral infections
Martinic, M. M. A., & von Herrath, M. G. (2008) · Trends in Immunology · doi:10.1016/j.it.2007.12.002 · Cited by 32 · see citing works
The road to recovery: translating PD-1 biology into clinical benefit
Riley, J. L., & June, C. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.12.001 · Cited by 30 · see citing works
Self-citation
Regulation of cell signaling by the protein tyrosine phosphatases, CD45 and SHP-1
Ulyanova, T., Blasioli, J., & Thomas, M. L. (1997) · Immunologic Research · doi:10.1007/bf02786326 · Cited by 25 · see citing works
The interchain disulfide linkage is not a prerequisite but enhances CD28 costimulatory function
Lázár‐Molnár, E., Almo, S. C., & Nathenson, S. G. (2006) · Cellular Immunology · doi:10.1016/j.cellimm.2007.02.014 · Cited by 23 · see citing works

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Research works printed but not linked: 5

[8]Okazaki T Honjo T The PD-1-PD-L pathway in immunological tolerance Trends Immunol 2006 27 195 201 16500147
[26]Riley JL June CH The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation Blood 2005 105 13 21 15353480
[27]Okazaki T Honjo T The PD-1-PD-L pathway in immunological tolerance Trends Immunol 2006 27 195 201 16500147
[52]Okazaki T Maeda A Nishimura H Kurosaki T Honjo T PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine Proc Natl Acad Sci U S A 2001 98 13866 13871 11698646 PMC61133
[98]Sharpe AH Freeman GJ The B7-CD28 superfamily Nat Rev Immunol 2002 2 116 126 11910893

Sorted by citations

Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652 · see citing works
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114 · see citing works
Overview of the immune response
Chaplin, D. D. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.12.980 · Cited by 2,235 · see citing works
The PD‐1 pathway in tolerance and autoimmunity
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00923.x · Cited by 2,300 · see citing works
The diverse functions of the PD1 inhibitory pathway
Sharpe, A. H., & Pauken, K. E. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.108 · Cited by 1,980 · see citing works
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689 · see citing works
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2
Yokosuka, T., Takamatsu, M., Kobayashi-Imanishi, W., Hashimoto-Tane, A., Azuma, M., & Saito, T. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112741 · Cited by 1,161 · see citing works
Overcoming T cell exhaustion in infection and cancer
Pauken, K. E., & Wherry, E. J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.008 · Cited by 1,178 · see citing works
T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
Crespo, J., Sun, H., Welling, T. H., Tian, Z., & Zou, W. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.12.003 · Cited by 752 · see citing works
Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors
Duraiswamy, J., Kaluza, K. M., Freeman, G. J., & Coukos, G. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4100 · Cited by 737 · see citing works
Small RNAs are modified with N-glycans and displayed on the surface of living cells
Flynn, R. A., Pedram, K., Malaker, S. A., Batista, P. J., Smith, B. A. H., Johnson, A. G., George, B. M., Majzoub, K., Villalta, P. W., Carette, J. E., et al. (2021) · Cell · doi:10.1016/j.cell.2021.04.023 · Cited by 648 · see citing works
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Kleffel, S., Posch, C., Barthel, S. R., Mueller, H., Schlapbach, C., Guenova, E., Elco, C. P., Lee, N., Juneja, V. R., Zhan, Q., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.052 · Cited by 648 · see citing works
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Su, Y., Chen, D., Yuan, D., Lausted, C. G., Choi, J., Dai, C. L., Voillet, V., Duvvuri, V. R. S. K., Scherler, K., Troisch, P., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.037 · Cited by 591 · see citing works
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DePeaux, K., & Delgoffe, G. M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00541-y · Cited by 614 · see citing works
The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation
Bardhan, K., Anagnostou, T., & Boussiotis, V. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00550 · Cited by 606 · see citing works
Deciphering and Reversing Tumor Immune Suppression
Motz, G. T., & Coukos, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.005 · Cited by 600 · see citing works
Cutting Edge: TIGIT Has T Cell-Intrinsic Inhibitory Functions
Joller, N., Hafler, J. P., Brynedal, B., Kassam, N., Spoerl, S., Levin, S. D., Sharpe, A. H., & Kuchroo, V. K. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003081 · Cited by 574 · see citing works
The pharmacology of second-generation chimeric antigen receptors
van der Stegen, S. J. C., Hamieh, M., & Sadelain, M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4597 · Cited by 562 · see citing works
Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis
Beauchemin, N., & Arabzadeh, A. (2013) · Cancer and Metastasis Reviews · doi:10.1007/s10555-013-9444-6 · Cited by 544 · see citing works
How Tolerogenic Dendritic Cells Induce Regulatory T Cells
Maldonado, R., & von Andrian, U. H. (2010) · Advances in immunology · doi:10.1016/b978-0-12-380995-7.00004-5 · Cited by 543 · see citing works
The immunological synapse
Dustin, M. L. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0161 · Cited by 502 · see citing works
Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints
Chang, L., Barroso‐Sousa, R., Tolaney, S. M., Hodi, F. S., Kaiser, U. B., & Min, L. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00006 · Cited by 546 · see citing works
Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond
Ai, L., Xu, A., & Xu, J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-3266-5_3 · Cited by 531 · see citing works
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF
Quigley, M. M., Pereyra, F., Nilsson, B., Porichis, F., Fonseca, C., Eichbaum, Q. G., Jülg, B. D., Jesneck, J. L., Brosnahan, K., Imam, S., et al. (2010) · Nature Medicine · doi:10.1038/nm.2232 · Cited by 505 · see citing works
PD‐1/PD‐L1 immune checkpoint: Potential target for cancer therapy
Dermani, F. K., Samadi, P., Rahmani, G., Kohlan, A. K., & Najafi, R. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27172 · Cited by 509 · see citing works
Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells
Odorizzi, P. M., Pauken, K. E., Paley, M., Sharpe, A. H., & Wherry, E. J. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20142237 · Cited by 464 · see citing works
Functional Anatomy of T Cell Activation and Synapse Formation
Fooksman, D., Vardhana, S. A., Vasiliver-Shamis, G., Liese, J., Blair, D. A., Waite, J. C., Sacristán, C., Victora, G. D., Zanin‐Zhorov, A., & Dustin, M. L. (2009) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101308 · Cited by 449 · see citing works
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Youngblood, B., Oestreich, K. J., Ha, S., Duraiswamy, J., Akondy, R. S., West, E. E., Wei, Z., Lu, P., Austin, J. W., Riley, J. L., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.06.015 · Cited by 418 · see citing works
Self-citation
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He, J., Hu, Y., Hu, M., & Li, B. (2015) · Scientific Reports · doi:10.1038/srep13110 · Cited by 402 · see citing works
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Gumber, D., & Wang, L. D. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103941 · Cited by 409 · see citing works
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Madore, J., Vilain, R. E., Menzies, A. M., Kakavand, H., Wilmott, J. S., Hyman, J., Yearley, J. H., Kefford, R. F., Thompson, J. F., Long, G. V., et al. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12340 · Cited by 396 · see citing works
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Staron, M. M., Gray, S. M., Marshall, H. D., Parish, I. A., Chen, J. H., Perry, C. J., Cui, G., Li, M. O., & Kaech, S. M. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.013 · Cited by 384 · see citing works
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Gray, M. A., Stanczak, M. A., Mantuano, N. R., Xiao, H., Pijnenborg, J. F. A., Malaker, S. A., Miller, C. L., Weidenbacher, P. A. B., Tanzo, J. T., Ahn, G., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0622-x · Cited by 373 · see citing works
At the Bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy
Intlekofer, A. M., & Thompson, C. B. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.1212621 · Cited by 374 · see citing works
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Liu, Y., Cheng, Y., Xu, Y., Wang, Z., Du, X., Li, C., Peng, J., Gao, L., Liang, X., & Ma, C. (2017) · Oncogene · doi:10.1038/onc.2017.209 · Cited by 367 · see citing works
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Han, X., Wang, M., Duan, S., Franco, P. J., Kenty, J. H.-R., Hedrick, P., Xia, Y., Allen, A., Ferreira, L. M. R., Strominger, J. L., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902566116 · Cited by 363 · see citing works
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Sharpe, A. H. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00784.x · Cited by 359 · see citing works
The promise and challenges of immune agonist antibody development in cancer
Mayes, P. A., Hance, K. W., & Hoos, A. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.75 · Cited by 355 · see citing works
T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses
Saeidi, A., Zandi, K., Cheok, Y. Y., Saeidi, H., Wong, W. F., Lee, C. Y. Q., Cheong, H. C., Yong, Y. K., Larsson, M., & Shankar, E. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02569 · Cited by 346 · see citing works
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Dong, Y., Sun, Q., & Zhang, X. (2016) · Oncotarget · doi:10.18632/oncotarget.13895 · Cited by 339 · see citing works
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Webb, J. R., Milne, K., Kroeger, D. R., & Nelson, B. H. (2016) · Gynecologic Oncology · doi:10.1016/j.ygyno.2016.03.008 · Cited by 335 · see citing works
Programmed Death Ligand 2 in Cancer-Induced Immune Suppression
Rozali, E. N., Hato, S. V., Robinson, B. W. S., Lake, R., & Lesterhuis, W. J. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/656340 · Cited by 326 · see citing works
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Cheng, X., Veverka, V., Radhakrishnan, A., Waters, L. C., Muskett, F. W., Morgan, S. H., Huo, J., Yu, C., Evans, E. J., Leslie, A. J., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.448126 · Cited by 325 · see citing works
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Kurachi, M. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-019-00744-5 · Cited by 317 · see citing works
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Riera-Domingo, C., Audigé, A., Granja, S., Cheng, W.-C., Ho, P.-C., Baltazar, F., Stockmann, C., & Mazzone, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00018.2019 · Cited by 310 · see citing works
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Globig, A.-M., Zhao, S., Roginsky, J., Maltez, V. I., Güiza, J., Avina-Ochoa, N., Heeg, M., Hoffmann, F. A., Chaudhary, O., Wang, J., et al. (2023) · Nature · doi:10.1038/s41586-023-06568-6 · Cited by 317 · see citing works
Strength of PD-1 signaling differentially affects T-cell effector functions
Wei, F., Zhong, S., Ma, Z., Kong, H., Medvec, A. R., Ahmed, R., Freeman, G. J., Krogsgaard, M., & Riley, J. L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305394110 · Cited by 306 · see citing works
Self-citation
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Nirschl, C. J., & Drake, C. G. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1972 · Cited by 308 · see citing works
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Ghosh, C., Luong, G., & Sun, Y. (2021) · Journal of Cancer · doi:10.7150/jca.57334 · Cited by 298 · see citing works
Phosphotyrosine-Dependent Coupling of Tim-3 to T-Cell Receptor Signaling Pathways
Lee, J., Su, E. W., Zhu, C., Hainline, S., Phuah, J., Moroco, J. A., Smithgall, T. E., Kuchroo, V. K., & Kane, L. P. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05297-11 · Cited by 285 · see citing works
Bacterial Outer Membrane Vesicles Presenting Programmed Death 1 for Improved Cancer Immunotherapy via Immune Activation and Checkpoint Inhibition
Li, Y., Zhao, R., Cheng, K., Zhang, K., Wang, Y., Zhang, Y., Li, Y., Liu, G., Xu, J., Xu, J., et al. (2020) · ACS Nano · doi:10.1021/acsnano.0c03776 · Cited by 281 · see citing works
Radiotherapy Increases the Permissiveness of Established Mammary Tumors to Rejection by Immunomodulatory Antibodies
Verbrugge, I., Hagekyriakou, J., Sharp, L. L., Gallí, M., West, A. C., McLaughlin, N. M., Duret, H., Yagita∥, H., Johnstone, R. W., Smyth, M. J., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0210 · Cited by 275 · see citing works
Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity
Gianchecchi, E., Delfino, D. V., & Fierabracci, A. (2013) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.05.003 · Cited by 270 · see citing works
Programmed death-1 pathway in cancer and autoimmunity
Pedoeem, A., Azoulay‐Alfaguter, I., Strazza, M., Silverman, G. J., & Mor, A. (2014) · Clinical Immunology · doi:10.1016/j.clim.2014.04.010 · Cited by 269 · see citing works
Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity
Schnell, A., Huang, L., Singer, M., Singaraju, A., Barilla, R. M., Regan, B. M. L., Bollhagen, A., Thakore, P. I., Dionne, D., Delorey, T. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.018 · Cited by 268 · see citing works
PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance
Tan, C. L., Kuchroo, J. R., Sage, P. T., Liang, D., Francisco, L. M., Buck, J. N., Thaker, Y. R., Zhang, Q., McArdel, S. L., Juneja, V. R., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20182232 · Cited by 252 · see citing works
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Attanasio, J., & Wherry, E. J. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.022 · Cited by 256 · see citing works
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Wartewig, T., Kurgyis, Z., Keppler, S. J., Pechloff, K., Hameister, E., Öllinger, R., Maresch, R., Buch, T., Steiger, K., Winter, C., et al. (2017) · Nature · doi:10.1038/nature24649 · Cited by 253 · see citing works
Immunotherapy for triple-negative breast cancer: Existing challenges and exciting prospects
Jia, H., Truica, C. I., Wang, B., Wang, Y., Ren, X., Harvey, H. A., Song, J. J., & Yang, J. (2017) · Drug Resistance Updates · doi:10.1016/j.drup.2017.07.002 · Cited by 241 · see citing works
VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy
Yuan, L., Tatineni, J., Mahoney, K. M., & Freeman, G. J. (2021) · Trends in Immunology · doi:10.1016/j.it.2020.12.008 · Cited by 227 · see citing works
A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy
Leone, R. D., Lo, Y.-C., & Powell, J. D. (2015) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2015.03.008 · Cited by 224 · see citing works
Tumor innervation: peripheral nerves take control of the tumor microenvironment
Gysler, S. M., & Drapkin, R. (2021) · Journal of Clinical Investigation · doi:10.1172/jci147276 · Cited by 227 · see citing works
Neutrophils as potential therapeutic targets in hepatocellular carcinoma
Geh, D., Leslie, J., Rumney, R., Reeves, H. L., Bird, T. G., & Mann, D. A. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00568-5 · Cited by 222 · see citing works
Therapy for metastatic melanoma: the past, present, and future
Finn, L. E., Markovic, S. N., & Joseph, R. W. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-23 · Cited by 217 · see citing works
PD-1 Increases PTEN Phosphatase Activity While Decreasing PTEN Protein Stability by Inhibiting Casein Kinase 2
Patsoukis, N., Li, L., Sari, D., Petkova, V., & Boussiotis, V. A. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00319-13 · Cited by 187 · see citing works
Biochemical Signaling of PD-1 on T Cells and Its Functional Implications
Boussiotis, V. A., Chatterjee, P., & Li, L. (2014) · The Cancer Journal · doi:10.1097/ppo.0000000000000059 · Cited by 186 · see citing works
Anti‐PD‐1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases
Dhupkar, P. M., Gordon, N. B., Stewart, J., & Kleinerman, E. S. (2018) · Cancer Medicine · doi:10.1002/cam4.1518 · Cited by 182 · see citing works
Clonal deletion and the fate of autoreactive thymocytes that survive negative selection
Pobezinsky, L. A., Angelov, G. S., Tai, X., Jeurling, S., Laethem, F. V., Feigenbaum, L., Park, J., & Singer, A. (2012) · Nature Immunology · doi:10.1038/ni.2292 · Cited by 179 · see citing works
Novel Radiotracer for ImmunoPET Imaging of PD-1 Checkpoint Expression on Tumor Infiltrating Lymphocytes
Natarajan, A., Mayer, A. T., Xu, L., Reeves, R. E., Gano, J. J., & Gambhir, S. S. (2015) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.5b00318 · Cited by 167 · see citing works
Inhibitory Receptors on Lymphocytes: Insights from Infections
Odorizzi, P. M., & Wherry, E. J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1100038 · Cited by 168 · see citing works
Targeting Glycosylated PD-1 Induces Potent Antitumor Immunity
Sun, L., Li, C.-W., Chung, E. M., Yang, R., Kim, Y., Park, A. H., Lai, Y., Yang, Y., Wang, Y.-H., Liu, J., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-3133 · Cited by 167 · see citing works
Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches
Fisicaro, P., Barili, V., Rossi, M., Montali, I., Vecchi, A. L., Acerbi, G., Laccabue, D., Zecca, A., Penna, A., Missale, G., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00849 · Cited by 165 · see citing works
PD-1 and cancer: molecular mechanisms and polymorphisms
Salmaninejad, A., Khoramshahi, V., Azani, A., Soltaninejad, E., Aslani, S., Zamani, M. R., Zal, M., Nesaei, A., & Hosseini, S. M. (2017) · Immunogenetics · doi:10.1007/s00251-017-1015-5 · Cited by 160 · see citing works
High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells
Myklebust, J. H., Irish, J. M., Brody, J., Czerwinski, D. K., Houot, R., Kohrt, H. E. K., Timmerman, J. M., SAID, J. W., Green, M. R., Delabie, J., et al. (2013) · Blood · doi:10.1182/blood-2012-04-421826 · Cited by 158 · see citing works
Immune suppression and reversal of the suppressive tumor microenvironment
Shimizu, K., Iyoda, T., Okada, M., Yamasaki, S., & Fujii, S. (2018) · International Immunology · doi:10.1093/intimm/dxy042 · Cited by 159 · see citing works
Bystander T cells in cancer immunology and therapy
Meier, S. L., Satpathy, A. T., & Wells, D. K. (2022) · Nature Cancer · doi:10.1038/s43018-022-00335-8 · Cited by 157 · see citing works
Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy
Celis-Gutierrez, J., Blattmann, P., Zhai, Y., Jarmuzynski, N., Ruminski, K., Grégoire, C., Ounoughene, Y., Fiore, F., Aebersold, R., Roncagalli, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.041 · Cited by 154 · see citing works
<p>Blocking TGF-β Signaling To Enhance The Efficacy Of Immune Checkpoint Inhibitor</p>
Bai, X., Yi, M., Jiao, Y., Chu, Q., & Wu, K. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s224013 · Cited by 153 · see citing works
Immunosuppressive Effects of Multiple Myeloma Are Overcome by PD-L1 Blockade
Hallett, W. H. D., Jing, W., Drobyski, W. R., & Johnson, B. D. (2011) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2011.03.011 · Cited by 152 · see citing works
Blockade of PD‐1 or p38 MAP kinase signaling enhances senescent human CD8<sup>+</sup> T‐cell proliferation by distinct pathways
Henson, S. M., Macaulay, R., Riddell, N. E., Nunn, C. J., & Akbar, A. N. (2015) · European Journal of Immunology · doi:10.1002/eji.201445312 · Cited by 146 · see citing works
Dose-Dependent Effect of Anti-CTLA-4 on Survival in Sepsis
Inoue, S., Bo, L., Bian, J., Unsinger, J., Chang, K. C., & Hotchkiss, R. S. (2011) · Shock · doi:10.1097/shk.0b013e3182168cce · Cited by 151 · see citing works
CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction
Peretz, Y., He, Z., Shi, Y., Yassine‐Diab, B., Goulet, J.-P., Bordi, R., Filali‐Mouhim, A., Loubert, J.-B., Far, M. E., Dupuy, F. P., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002840 · Cited by 148 · see citing works
A Mini-Review for Cancer Immunotherapy: Molecular Understanding of PD-1/PD-L1 Pathway & Translational Blockade of Immune Checkpoints
Li, Y., Li, F., Jiang, F., Lv, X., Zhang, R., Lü, A., & Zhang, G. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17071151 · Cited by 147 · see citing works
The three main stumbling blocks for anticancer T cells
Baitsch, L., Marraco, S. A. F., Legat, A., Meyer, C., & Speiser, D. E. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.02.006 · Cited by 144 · see citing works
ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis
Moguche, A. O., Shafiani, S., Clemons, C., Larson, R. P., Dinh, C., Higdon, L. E., Cambier, C. J., Sissons, J. R., Gallegos, A. M., Fink, P. J., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20141518 · Cited by 140 · see citing works
Exhaustion of T lymphocytes in the tumor microenvironment: Significance and effective mechanisms
Gholami, M. D., Kardar, G. A., Saeedi, Y., Heidari, S., Garssen, J., & Falak, R. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.10.002 · Cited by 140 · see citing works
Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression
Khanam, A., Chua, J. V., & Kottilil, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115497 · Cited by 138 · see citing works
Current and future perspectives of PD-1/PDL-1 blockade in cancer immunotherapy
Makuku, R., Khalili, N., Razi, S., Keshavarz-Fathi, M., & Rezaei, N. (2021) · Journal of Immunology Research · doi:10.1155/2021/6661406 · Cited by 136 · see citing works
Regulatory B cells in anti-tumor immunity
Zhang, Y., Gallastegui, N., & Rosenblatt, J. D. (2015) · International Immunology · doi:10.1093/intimm/dxv034 · Cited by 133 · see citing works
PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2
Xu, X., Hou, B., Fulzele, A., Masubuchi, T., Zhao, Y., Wu, Z., Hu, Y., Jiang, Y., Ma, Y., Wang, H., et al. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.201905085 · Cited by 131 · see citing works
Orchestrating immune check-point blockade for cancer immunotherapy in combinations
Perez‐Gracia, J. L., Labiano, S., Rodriguez-Ruiz, M. E., Sanmamed, M. F., & Melero, I. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.01.002 · Cited by 128 · see citing works
Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia
Christiansson, L. H., Söderlund, S., Svensson, E., Mustjoki, S. M., Bengtsson, M., Simonsson, B., Olsson‐Strömberg, U., & Loskog, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055818 · Cited by 129 · see citing works
Functional Expression of Programmed Death-Ligand 1 (B7-H1) by Immune Cells and Tumor Cells
Johnson, R. M. G., & Dong, H. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00961 · Cited by 127 · see citing works
Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors
Dutta, S., Ganguly, A., Chatterjee, K., Spada, S., & Mukherjee, S. (2023) · Biology · doi:10.3390/biology12020218 · Cited by 134 · see citing works
PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation
Petrelli, A., Mijnheer, G., van Konijnenburg, D. P. H., van der Wal, M. M., Giovannone, B., Mocholi, E., Vazirpanah, N., Broen, J. C., Hijnen, D., Oldenburg, B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96107 · Cited by 126 · see citing works
Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC)
Incorvaia, L., Fanale, D., Badalamenti, G., Barraco, N., Bono, M., Corsini, L. R., Galvano, A., Gristina, V., Listì, A., Vieni, S., et al. (2019) · Advances in Therapy · doi:10.1007/s12325-019-01057-7 · Cited by 126 · see citing works
Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy.
Flies, D. B., Sandler, B. J., Sznol, M., & Chen, L. (2011) · Europe PMC (PubMed Central) · Cited by 123 · see citing works
Immune receptor inhibition through enforced phosphatase recruitment
Fernandes, R. A., Su, L., Nishiga, Y., Ren, J., Bhuiyan, M. A., Cheng, N., Kuo, C. J., Picton, L. K., Ohtsuki, S., Majzner, R. G., et al. (2020) · Nature · doi:10.1038/s41586-020-2851-2 · Cited by 124 · see citing works
Immune Checkpoint Inhibition in Head and Neck Cancer
Forster, M. D., & Devlin, M.-J. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00310 · Cited by 121 · see citing works
Programmed death‐ligand 1 expression at tumor invasive front is associated with epithelial‐mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma
Tsutsumi, S., Saeki, H., Nakashima, Y., Ito, S., Oki, E., Morita, M., Oda, Y., Okano, S., & Maehara, Y. (2017) · Cancer Science · doi:10.1111/cas.13237 · Cited by 119 · see citing works

Role of PD-1 in Regulating T-Cell Immunity
Jin, H., Ahmed, R., & Okazaki, T. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_116 · Cited by 303 · see citing works
Signaling via PD-1 controls the expression of cyclins and the activation of cdk2 in human primary CD4+ T cells (50.30)
Brown, J. A., & Boussiotis, V. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.184.supp.50.30
Contribution of the PD‐1 ligands/PD‐1 signaling pathway to dendritic cell‐mediated CD4 + T cell activation
Kuipers, 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 · see citing works
The research development of PD-1/PD-L1 signaling pathway in multi-system disease
Liu, J. (2013) · Medical Journal of West China
Research Progress in PD-1/PD-L Co-inhibitory Signaling Pathway
Wu, Y. (2010)

Authors: Riley, J. L.
Affiliations: University of Pennsylvania (US)
Corresponding author: Riley, James L.
ORCID: Riley, James L.
Venue: Immunological Reviews
Publisher: Wiley
Published: 2009-04-21
Volume: 229
Issue: 1
Pages: 114-125
ISSN: 0105-2896 (ISSN-L)
1600-065X
DOI: 10.1111/j.1600-065x.2009.00767.x
PMC: PMC3424066
OpenAlex: W2017712207
Cited by: 778
References: 95
Citations by year: 2026: 21 · 2025: 39 · 2024: 37 · 2023: 66 · 2022: 73 · 2021: 84 · 2020: 64 · 2019: 61 · 2018: 60 · 2017: 49 · 2016: 33 · 2015: 41 · 2014: 34 · 2013: 37 · 2012: 30
FWCI: 2.32
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunological Reviews (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (CA113783, R01CA113783)
National Institute of Allergy and Infectious Diseases (AI080192, P01AI080192, R01AI057838, AI057838, PD-1 PO1AI080192)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords: PD-1 signaling, PDCD1, PD-L1, PD-L2, T cell exhaustion, T cell proliferation inhibition, cytotoxic T lymphocyte antigen 4, signal transduction, T cell differentiation, immune checkpoint, primary T cells
MeSH terms: Animals, Antigens, Surface, Humans, T-Lymphocytes, Signal Transduction, Antigens, CD, CD28 Antigens, Apoptosis Regulatory Proteins, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 11, CTLA-4 Antigen, Programmed Cell Death 1 Receptor

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