Journal Article
. 2020 Oct; 218(1):.
doi: 10.1084/jem.20182232.

PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance

Catherine L Tan 1 Juhi R Kuchroo 1 Peter T Sage 1 Dan Liang 1 Loise M Francisco 1 Jessica Buck 1 Youg Raj Thaker 1 Qianxia Zhang 2 Shannon L McArdel 1 Vikram R Juneja 1 Sun Jung Lee 1 Scott B Lovitch 1 Christine Lian 3 George F Murphy 3 Bruce R Blazar 4 Dario A A Vignali 2 Gordon J Freeman 5 Arlene H Sharpe 1 
Affiliations
  • PMID: 33045061
  •     70 References
  •     33 citations

Abstract

Inhibitory signals through the PD-1 pathway regulate T cell activation, T cell tolerance, and T cell exhaustion. Studies of PD-1 function have focused primarily on effector T cells. Far less is known about PD-1 function in regulatory T (T reg) cells. To study the role of PD-1 in T reg cells, we generated mice that selectively lack PD-1 in T reg cells. PD-1-deficient T reg cells exhibit an activated phenotype and enhanced immunosuppressive function. The in vivo significance of the potent suppressive capacity of PD-1-deficient T reg cells is illustrated by ameliorated experimental autoimmune encephalomyelitis (EAE) and protection from diabetes in nonobese diabetic (NOD) mice lacking PD-1 selectively in T reg cells. We identified reduced signaling through the PI3K-AKT pathway as a mechanism underlying the enhanced suppressive capacity of PD-1-deficient T reg cells. Our findings demonstrate that cell-intrinsic PD-1 restraint of T reg cells is a significant mechanism by which PD-1 inhibitory signals regulate T cell tolerance and autoimmunity.

Tissue expression of PD-L1 mediates peripheral T cell tolerance.
Mary E Keir, Spencer C Liang, +7 authors, Arlene H Sharpe.
J Exp Med, 2006 Apr 12; 203(4). PMID: 16606670    Free PMC article.
Highly Cited.
PD-1 increases PTEN phosphatase activity while decreasing PTEN protein stability by inhibiting casein kinase 2.
Nikolaos Patsoukis, Lequn Li, +2 authors, Vassiliki A Boussiotis.
Mol Cell Biol, 2013 Jun 05; 33(16). PMID: 23732914    Free PMC article.
CD28 signals the differential control of regulatory T cells and effector T cells.
Norihisa Mikami, Shimon Sakaguchi.
Eur J Immunol, 2014 Mar 22; 44(4). PMID: 24652756
Treating human autoimmunity: current practice and future prospects.
Michael D Rosenblum, Iris K Gratz, Jonathan S Paw, Abul K Abbas.
Sci Transl Med, 2012 Mar 17; 4(125). PMID: 22422994    Free PMC article.
Review.
Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3.
Dapeng Yan, Julia Farache, +2 authors, Christophe Benoist.
Proc Natl Acad Sci U S A, 2015 Dec 03; 112(48). PMID: 26627244    Free PMC article.
PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells.
Yvette E Latchman, Spencer C Liang, +6 authors, Arlene H Sharpe.
Proc Natl Acad Sci U S A, 2004 Jul 14; 101(29). PMID: 15249675    Free PMC article.
Highly Cited.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function.
Nathan L Price, Ana P Gomes, +19 authors, David A Sinclair.
Cell Metab, 2012 May 09; 15(5). PMID: 22560220    Free PMC article.
Highly Cited.
Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells.
Li Wang, Karina Pino-Lagos, +3 authors, Randolph J Noelle.
Proc Natl Acad Sci U S A, 2008 Jul 05; 105(27). PMID: 18599457    Free PMC article.
Highly Cited.
Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces.
Yuri P Rubtsov, Jeffrey P Rasmussen, +9 authors, Alexander Y Rudensky.
Immunity, 2008 Apr 05; 28(4). PMID: 18387831
Highly Cited.
How regulatory T cells work.
Dario A A Vignali, Lauren W Collison, Creg J Workman.
Nat Rev Immunol, 2008 Jun 21; 8(7). PMID: 18566595    Free PMC article.
Highly Cited. Review.
Restoring function in exhausted CD8 T cells during chronic viral infection.
Daniel L Barber, E John Wherry, +5 authors, Rafi Ahmed.
Nature, 2005 Dec 31; 439(7077). PMID: 16382236
Highly Cited.
The PDL1-PD1 axis converts human TH1 cells into regulatory T cells.
Shoba Amarnath, Courtney W Mangus, +11 authors, Daniel H Fowler.
Sci Transl Med, 2011 Dec 03; 3(111). PMID: 22133721    Free PMC article.
Highly Cited.
Regulatory T cells: mechanisms of differentiation and function.
Steven Z Josefowicz, Li-Fan Lu, Alexander Y Rudensky.
Annu Rev Immunol, 2012 Jan 10; 30. PMID: 22224781    Free PMC article.
Highly Cited. Review.
Targeting T Cell Co-receptors for Cancer Therapy.
Margaret K Callahan, Michael A Postow, Jedd D Wolchok.
Immunity, 2016 May 19; 44(5). PMID: 27192570
Highly Cited. Review.
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR.
Stephan Sauer, Ludovica Bruno, +10 authors, Matthias Merkenschlager.
Proc Natl Acad Sci U S A, 2008 May 30; 105(22). PMID: 18509048    Free PMC article.
Highly Cited.
Control of regulatory T cell development by the transcription factor Foxp3.
Shohei Hori, Takashi Nomura, Shimon Sakaguchi.
Science, 2003 Jan 11; 299(5609). PMID: 12522256
Highly Cited.
mTOR signaling, Tregs and immune modulation.
Nicole M Chapman, Hongbo Chi.
Immunotherapy, 2014 Dec 20; 6(12). PMID: 25524385    Free PMC article.
Review.
Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.
Jian Wang, Taku Yoshida, +3 authors, Tasuku Honjo.
Proc Natl Acad Sci U S A, 2005 Aug 10; 102(33). PMID: 16087865    Free PMC article.
Highly Cited.
Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells.
Natasha K Crellin, Rosa V Garcia, Megan K Levings.
Blood, 2006 Oct 26; 109(5). PMID: 17062729
PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation.
Nikolaos Patsoukis, Kankana Bardhan, +9 authors, Vassiliki A Boussiotis.
Nat Commun, 2015 Mar 27; 6. PMID: 25809635    Free PMC article.
Highly Cited.
PD-1 signaling in primary T cells.
James L Riley.
Immunol Rev, 2009 May 12; 229(1). PMID: 19426218    Free PMC article.
Highly Cited. Review.
Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses.
Spencer C Liang, Yvette E Latchman, +4 authors, Arlene H Sharpe.
Eur J Immunol, 2003 Sep 30; 33(10). PMID: 14515254
Highly Cited.
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells.
Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman.
Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248
Highly Cited.
Suppression by TFR cells leads to durable and selective inhibition of B cell effector function.
Peter T Sage, Noga Ron-Harel, +8 authors, Arlene H Sharpe.
Nat Immunol, 2016 Nov 01; 17(12). PMID: 27695002    Free PMC article.
Highly Cited.
Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability.
Alexandria Huynh, Michel DuPage, +9 authors, Laurence A Turka.
Nat Immunol, 2015 Jan 07; 16(2). PMID: 25559257    Free PMC article.
Highly Cited.
AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival.
Rigel J Kishton, Carson E Barnes, +15 authors, Jeffrey C Rathmell.
Cell Metab, 2016 Apr 15; 23(4). PMID: 27076078    Free PMC article.
Highly Cited.
Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death.
Hakryul Jo, Subhanjan Mondal, +11 authors, Hongbo R Luo.
Proc Natl Acad Sci U S A, 2012 Jun 13; 109(26). PMID: 22689977    Free PMC article.
Highly Cited.
Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation.
Nikolaos Patsoukis, Julia Brown, +3 authors, Vassiliki A Boussiotis.
Sci Signal, 2012 Jun 29; 5(230). PMID: 22740686    Free PMC article.
Highly Cited.
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
Jason D Fontenot, Marc A Gavin, Alexander Y Rudensky.
Nat Immunol, 2003 Mar 04; 4(4). PMID: 12612578
Highly Cited.
Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.
Suzanne L Topalian, Mario Sznol, +18 authors, F Stephen Hodi.
J Clin Oncol, 2014 Mar 05; 32(10). PMID: 24590637    Free PMC article.
Highly Cited.
Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis.
Alan D Salama, Tanuja Chitnis, +7 authors, Samia J Khoury.
J Exp Med, 2003 Jul 09; 198(1). PMID: 12847138    Free PMC article.
Highly Cited.
Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses.
Nicole Joller, Ester Lozano, +13 authors, Vijay K Kuchroo.
Immunity, 2014 Apr 22; 40(4). PMID: 24745333    Free PMC article.
Highly Cited.
Oestrogen modulates experimental autoimmune encephalomyelitis and interleukin-17 production via programmed death 1.
Chunhe Wang, Babak Dehghani, +3 authors, Halina Offner.
Immunology, 2009 Mar 24; 126(3). PMID: 19302141    Free PMC article.
Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade.
Erika D Reynoso, Kutlu G Elpek, +5 authors, Shannon J Turley.
J Immunol, 2009 Feb 10; 182(4). PMID: 19201863    Free PMC article.
Immunology beats cancer: a blueprint for successful translation.
Drew M Pardoll.
Nat Immunol, 2012 Nov 20; 13(12). PMID: 23160205    Free PMC article.
T cells in the control of organ-specific autoimmunity.
Jeffrey A Bluestone, Hélène Bour-Jordan, Mickie Cheng, Mark Anderson.
J Clin Invest, 2015 May 20; 125(6). PMID: 25985270    Free PMC article.
Review.
Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression.
Valerie A Gerriets, Rigel J Kishton, +10 authors, Jeffrey C Rathmell.
Nat Immunol, 2016 Nov 01; 17(12). PMID: 27695003    Free PMC article.
Highly Cited.
T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition.
Enfu Hui, Jeanne Cheung, +8 authors, Ronald D Vale.
Science, 2017 Mar 11; 355(6332). PMID: 28280247    Free PMC article.
Highly Cited.
CTLA-4 control over Foxp3+ regulatory T cell function.
Kajsa Wing, Yasushi Onishi, +5 authors, Shimon Sakaguchi.
Science, 2008 Oct 11; 322(5899). PMID: 18845758
Highly Cited.
Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton.
Hai Hu, Ashish Juvekar, +15 authors, Gerburg M Wulf.
Cell, 2016 Jan 30; 164(3). PMID: 26824656    Free PMC article.
Highly Cited.
Overcoming T cell exhaustion in infection and cancer.
Kristen E Pauken, E John Wherry.
Trends Immunol, 2015 Mar 24; 36(4). PMID: 25797516    Free PMC article.
Highly Cited. Review.
PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy.
Sandip Pravin Patel, Razelle Kurzrock.
Mol Cancer Ther, 2015 Feb 20; 14(4). PMID: 25695955
Highly Cited. Review.
Regulatory T-cell homeostasis: steady-state maintenance and modulation during inflammation.
Kate S Smigiel, Shivani Srivastava, J Michael Stolley, Daniel J Campbell.
Immunol Rev, 2014 Apr 10; 259(1). PMID: 24712458    Free PMC article.
Highly Cited. Review.
Accelerated course of experimental autoimmune encephalomyelitis in PD-1-deficient central nervous system myelin mutants.
Antje Kroner, Nicholas Schwab, +6 authors, Heinz Wiendl.
Am J Pathol, 2009 May 16; 174(6). PMID: 19443704    Free PMC article.
PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer.
Jennifer H Yearley, Christopher Gibson, +10 authors, Terrill McClanahan.
Clin Cancer Res, 2017 Jun 18; 23(12). PMID: 28619999
Highly Cited.
The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice.
Mohammed Javeed I Ansari, Alan D Salama, +9 authors, Mohamed H Sayegh.
J Exp Med, 2003 Jul 09; 198(1). PMID: 12847137    Free PMC article.
Highly Cited.
Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.
Baihao Zhang, Shunsuke Chikuma, +2 authors, Tasuku Honjo.
Proc Natl Acad Sci U S A, 2016 Jul 14; 113(30). PMID: 27410049    Free PMC article.
Highly Cited.
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.
Xuyu Zhou, Lukas T Jeker, +4 authors, Jeffrey A Bluestone.
J Exp Med, 2008 Aug 30; 205(9). PMID: 18725525    Free PMC article.
Highly Cited.
Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells.
Dean Franckaert, James Dooley, +7 authors, Susan M Schlenner.
Immunol Cell Biol, 2014 Dec 24; 93(4). PMID: 25533288    Free PMC article.
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms.
Richard V Parry, Jens M Chemnitz, +6 authors, James L Riley.
Mol Cell Biol, 2005 Oct 18; 25(21). PMID: 16227604    Free PMC article.
Highly Cited.
Tissue-expressed B7-H1 critically controls intestinal inflammation.
Lisa Scandiuzzi, Kaya Ghosh, +9 authors, Xingxing Zang.
Cell Rep, 2014 Feb 18; 6(4). PMID: 24529703    Free PMC article.
Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells.
Takahisa Miyao, Stefan Floess, +5 authors, Shohei Hori.
Immunity, 2012 Feb 14; 36(2). PMID: 22326580
Highly Cited.
The PD-1 pathway in tolerance and autoimmunity.
Loise M Francisco, Peter T Sage, Arlene H Sharpe.
Immunol Rev, 2010 Jul 20; 236. PMID: 20636820    Free PMC article.
Highly Cited. Review.
Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent.
Alice O Kamphorst, Andreas Wieland, +17 authors, Rafi Ahmed.
Science, 2017 Mar 11; 355(6332). PMID: 28280249    Free PMC article.
Highly Cited.
The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo.
Julianna Blagih, François Coulombe, +12 authors, Russell G Jones.
Immunity, 2015 Jan 22; 42(1). PMID: 25607458
Highly Cited.
Nivolumab plus ipilimumab in advanced melanoma.
Jedd D Wolchok, Harriet Kluger, +21 authors, Mario Sznol.
N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724867    Free PMC article.
Highly Cited.
Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family.
Hélène Bour-Jordan, Jonathan H Esensten, +3 authors, Jeffrey A Bluestone.
Immunol Rev, 2011 Apr 15; 241(1). PMID: 21488898    Free PMC article.
Highly Cited. Review.
Metabolic regulation of T lymphocytes.
Nancie J MacIver, Ryan D Michalek, Jeffrey C Rathmell.
Annu Rev Immunol, 2013 Jan 10; 31. PMID: 23298210    Free PMC article.
Highly Cited. Review.
The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells.
Sokol Haxhinasto, Diane Mathis, Christophe Benoist.
J Exp Med, 2008 Feb 20; 205(3). PMID: 18283119    Free PMC article.
Highly Cited.
T cell metabolism drives immunity.
Michael D Buck, David O'Sullivan, Erika L Pearce.
J Exp Med, 2015 Aug 12; 212(9). PMID: 26261266    Free PMC article.
Highly Cited. Review.
The programmed death-1 ligand 1:B7-1 pathway restrains diabetogenic effector T cells in vivo.
Alison M Paterson, Keturah E Brown, +7 authors, Arlene H Sharpe.
J Immunol, 2011 Jun 24; 187(3). PMID: 21697456    Free PMC article.
Migratory activity and functional changes of green fluorescent effector cells before and during experimental autoimmune encephalomyelitis.
A Flügel, T Berkowicz, +7 authors, H Wekerle.
Immunity, 2001 May 24; 14(5). PMID: 11371357
Highly Cited.
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells.
Loise M Francisco, Victor H Salinas, +4 authors, Arlene H Sharpe.
J Exp Med, 2009 Dec 17; 206(13). PMID: 20008522    Free PMC article.
Highly Cited.
A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application.
Taku Okazaki, Shunsuke Chikuma, +2 authors, Tasuku Honjo.
Nat Immunol, 2013 Nov 19; 14(12). PMID: 24240160
Highly Cited. Review.
The diverse functions of the PD1 inhibitory pathway.
Arlene H Sharpe, Kristen E Pauken.
Nat Rev Immunol, 2017 Oct 11; 18(3). PMID: 28990585
Highly Cited. Review.
PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta.
Kelly-Ann Sheppard, Lori J Fitz, +8 authors, Divya Chaudhary.
FEBS Lett, 2004 Sep 11; 574(1-3). PMID: 15358536
Highly Cited.
PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity.
Vikram R Juneja, Kathleen A McGuire, +5 authors, Arlene H Sharpe.
J Exp Med, 2017 Mar 18; 214(4). PMID: 28302645    Free PMC article.
Highly Cited.
Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy.
Dallas B Flies, Britt J Sandler, Mario Sznol, Lieping Chen.
Yale J Biol Med, 2011 Dec 20; 84(4). PMID: 22180678    Free PMC article.
Review.
Interferon-beta enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis.
Bettina Schreiner, Meike Mitsdoerffer, +4 authors, Heinz Wiendl.
J Neuroimmunol, 2004 Sep 03; 155(1-2). PMID: 15342209
Hyper-Progressive Disease: The Potential Role and Consequences of T-Regulatory Cells Foiling Anti-PD-1 Cancer Immunotherapy.
Christopher Tay, Yamin Qian, Shimon Sakaguchi.
Cancers (Basel), 2020 Dec 31; 13(1). PMID: 33375291    Free PMC article.
Review.
Immune checkpoint inhibitor-associated myocarditis: manifestations and mechanisms.
Javid Moslehi, Andrew H Lichtman, +2 authors, Richard N Kitsis.
J Clin Invest, 2021 Mar 02; 131(5). PMID: 33645548    Free PMC article.
Review.
Super-Treg: Toward a New Era of Adoptive Treg Therapy Enabled by Genetic Modifications.
Leila Amini, Jenny Greig, +6 authors, Ignacio Anegon.
Front Immunol, 2021 Mar 16; 11. PMID: 33717052    Free PMC article.
Review.
CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade.
Julie Vackova, Ingrid Polakova, Shweta Dilip Johari, Michal Smahel.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33923750    Free PMC article.
Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity.
Jenna L Collier, Sarah A Weiss, +2 authors, Arlene H Sharpe.
Nat Immunol, 2021 Jun 19; 22(7). PMID: 34140679
Review.
The Role of Programmed Death-1 in Type 1 Diabetes.
Christopher G Tucker, Alexander J Dwyer, Brian T Fife, Tijana Martinov.
Curr Diab Rep, 2021 May 07; 21(6). PMID: 33956235    Free PMC article.
Review.
TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer.
Zhouhong Ge, Maikel P Peppelenbosch, Dave Sprengers, Jaap Kwekkeboom.
Front Immunol, 2021 Aug 10; 12. PMID: 34367161    Free PMC article.
Review.
Lineage Reprogramming of Effector Regulatory T Cells in Cancer.
Michael L Dixon, Jonathan D Leavenworth, Jianmei W Leavenworth.
Front Immunol, 2021 Aug 17; 12. PMID: 34394124    Free PMC article.
Review.
Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease.
Justin Jacobse, Jing Li, +2 authors, Jeremy A Goettel.
Front Immunol, 2021 Aug 24; 12. PMID: 34421921    Free PMC article.
Review.
PI3-Kinase p110α Deficiency Modulates T Cell Homeostasis and Function and Attenuates Experimental Allergic Encephalitis in Mature Mice.
José M Rojo, María Montes-Casado, +3 authors, Pilar Portolés.
Int J Mol Sci, 2021 Aug 28; 22(16). PMID: 34445401    Free PMC article.
Fertility preservation and management of pregnancy in melanoma patients requiring systemic therapy.
J C Hassel, E Livingstone, +10 authors, C Berking.
ESMO Open, 2021 Aug 27; 6(5). PMID: 34438241    Free PMC article.
Review.
Regulation of autoreactive CD4 T cells by FoxO1 signaling in CNS autoimmunity.
Emma E Kraus, Laura Kakuk-Atkins, +3 authors, Yuhong Yang.
J Neuroimmunol, 2021 Aug 18; 359. PMID: 34403862    Free PMC article.
Impaired function of PD-1+ follicular regulatory T cells in systemic lupus erythematosus.
Izumi Kurata, Natsuko Mikami, +5 authors, Isao Matsumoto.
Clin Exp Immunol, 2021 Jul 10; 206(1). PMID: 34240405    Free PMC article.
Mechanism of action of PD-1 receptor/ligand targeted cancer immunotherapy.
Jannie Borst, Julia Busselaar, Douwe M T Bosma, Ferry Ossendorp.
Eur J Immunol, 2021 Jun 10; 51(8). PMID: 34106465    Free PMC article.
Review.
Glucocorticoid and PD-1 Cross-Talk: Does the Immune System Become Confused?
Sabrina Adorisio, Lorenza Cannarile, Domenico V Delfino, Emira Ayroldi.
Cells, 2021 Sep 29; 10(9). PMID: 34571982    Free PMC article.
Review.
Emerging concepts in PD-1 checkpoint biology.
Kristen E Pauken, James A Torchia, +2 authors, Gordon J Freeman.
Semin Immunol, 2021 May 20; 52. PMID: 34006473    Free PMC article.
Review.
Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma.
Sixue Liu, Hannah M Knochelmann, +16 authors, Roger S Lo.
Cell Rep Med, 2021 Nov 11; 2(10). PMID: 34755131    Free PMC article.
PI3Kδ Inhibitors as Immunomodulatory Agents for the Treatment of Lymphoma Patients.
Chiara Tarantelli, Lisa Argnani, Pier Luigi Zinzani, Francesco Bertoni.
Cancers (Basel), 2021 Nov 14; 13(21). PMID: 34771694    Free PMC article.
Review.
Remodeling of the tumor microenvironment via disrupting Blimp1+ effector Treg activity augments response to anti-PD-1 blockade.
Michael L Dixon, Lin Luo, +3 authors, Jianmei W Leavenworth.
Mol Cancer, 2021 Nov 21; 20(1). PMID: 34798898    Free PMC article.
Wnt-β-Catenin Signaling in Human Dendritic Cells Mediates Regulatory T-Cell Responses to Fungi via the PD-L1 Pathway.
Anupama Karnam, Srinivasa Reddy Bonam, +3 authors, Jagadeesh Bayry.
mBio, 2021 Nov 17; 12(6). PMID: 34781737    Free PMC article.
Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy.
Myeong Joon Kim, Sang-Jun Ha.
Front Cell Dev Biol, 2021 Dec 14; 9. PMID: 34901012    Free PMC article.
Review.
High-Fat Diet-Induced Fatty Liver Is Associated with Immunosuppressive Response during Sepsis in Mice.
Fangzhao Wang, Zhongran Cen, +6 authors, Peng Chen.
Oxid Med Cell Longev, 2021 Dec 21; 2021. PMID: 34925696    Free PMC article.
The foundations of immune checkpoint blockade and the ipilimumab approval decennial.
Alan J Korman, Sarah C Garrett-Thomson, Nils Lonberg.
Nat Rev Drug Discov, 2021 Dec 24;. PMID: 34937915
Review.
Potential Reasons for Unresponsiveness to Anti-PD1 Immunotherapy in Young Patients with Advanced Melanoma.
Devayani Machiraju, Sarah Schäfer, Jessica C Hassel.
Life (Basel), 2021 Dec 25; 11(12). PMID: 34947849    Free PMC article.
Review.
Monitoring PD-1 Phosphorylation to Evaluate PD-1 Signaling during Antitumor Immune Responses.
Xia Bu, Vikram R Juneja, +12 authors, Gordon J Freeman.
Cancer Immunol Res, 2021 Oct 13; 9(12). PMID: 34635486    Free PMC article.
Role of the tumor immune microenvironment in tumor immunotherapy.
Changsheng Zhou, Qianqian Liu, +2 authors, Wengang Li.
Oncol Lett, 2022 Jan 08; 23(2). PMID: 34992685    Free PMC article.
Review.
Reprogramming NK cells and macrophages via combined antibody and cytokine therapy primes tumors for elimination by checkpoint blockade.
Chensu Wang, Ang Cui, +11 authors, Darrell J Irvine.
Cell Rep, 2021 Nov 25; 37(8). PMID: 34818534    Free PMC article.
Neoantigens and their potential applications in tumor immunotherapy.
Xianzhu Fang, Zhiliang Guo, +4 authors, Hong Li.
Oncol Lett, 2022 Feb 08; 23(3). PMID: 35126730    Free PMC article.
Review.
Metabolic adaptation of lymphocytes in immunity and disease.
Nicole M Chapman, Hongbo Chi.
Immunity, 2022 Jan 13; 55(1). PMID: 35021054    Free PMC article.
Review.
Small spleen peptides prevent development of psoriatic arthritis via restoration of peripheral tolerance.
Viktor Wixler, Igor Z Zaytsev, +6 authors, Stephan Ludwig.
Mol Ther, 2021 Aug 28; 30(2). PMID: 34450252    Free PMC article.
The oxygen sensor prolyl hydroxylase domain 2 regulates the in vivo suppressive capacity of regulatory T cells.
Yousra Ajouaou, Abdulkader Azouz, +7 authors, Oberdan Leo.
Elife, 2022 Feb 23; 11. PMID: 35192456    Free PMC article.
Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer.
Menglu Dong, Quan Liu, Yi Xu, Qi Zhang.
Front Cell Dev Biol, 2022 Mar 19; 10. PMID: 35300426    Free PMC article.
Review.
Effects of PD-1 Signaling on Immunometabolic Reprogramming.
Vassiliki A Boussiotis, Nikolaos Patsoukis.
Immunometabolism, 2022 Apr 05; 4(2). PMID: 35371563    Free PMC article.