. 2020 Apr; 20(11):680-693.
doi: 10.1038/s41577-020-0296-3.

Modulation of regulatory T cell function and stability by co-inhibitory receptors

Liliana E Lucca 1 Margarita Dominguez-Villar 2 
  • PMID: 32269380
  •     187 References
  •     39 citations


Regulatory T (Treg) cells constitute a dynamic population that is essential for controlling immune responses in health and disease. Defects in Treg cell function and decreases in Treg cell numbers have been observed in patients with autoimmunity and the opposite effects on Treg cells occur in cancer settings. Current research on new therapies for these diseases is focused on modulating Treg cell function to increase or decrease suppressive activity in autoimmunity and cancer, respectively. In this regard, several co-inhibitory receptors that are preferentially expressed by Treg cells under homeostatic conditions have recently been shown to control Treg cell function and stability in different disease settings. These receptors could be amenable to therapeutic targeting aimed at modulating Treg cell function and plasticity. This Review summarizes recent data regarding the role of co-inhibitory molecules in the control of Treg cell function and stability, with a focus on their roles and potential therapeutic use in autoimmunity and cancer.

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Rosemarie H DeKruyff, Xia Bu, +9 authors, José M Casasnovas.
J Immunol, 2010 Jan 20; 184(4). PMID: 20083673    Free PMC article.
Highly Cited.
Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells.
Anne-Sophie Gautron, Margarita Dominguez-Villar, Marine de Marcken, David A Hafler.
Eur J Immunol, 2014 May 20; 44(9). PMID: 24838857    Free PMC article.
TIM3+FOXP3+ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer.
Kaori Sakuishi, Shin Foong Ngiow, +4 authors, Ana C Anderson.
Oncoimmunology, 2013 Jun 05; 2(4). PMID: 23734331    Free PMC article.
Highly Cited.
TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression.
Xin Gao, Yibei Zhu, +7 authors, Binfeng Lu.
PLoS One, 2012 Mar 01; 7(2). PMID: 22363469    Free PMC article.
Highly Cited.
Tim-3 expression defines regulatory T cells in human tumors.
Jing Yan, Yi Zhang, +3 authors, Limin Zheng.
PLoS One, 2013 Mar 26; 8(3). PMID: 23526963    Free PMC article.
Co-expression of LAG3 and TIM3 identifies a potent Treg population that suppresses macrophage functions in colorectal cancer patients.
Qiang Ma, Junning Liu, +4 authors, Yuantao Li.
Clin Exp Pharmacol Physiol, 2018 Jun 16; 45(10). PMID: 29905955
Ovarian carcinoma-infiltrating regulatory T cells were more potent suppressors of CD8(+) T cell inflammation than their peripheral counterparts, a function dependent on TIM3 expression.
Meimei Bu, Yizhen Shen, +4 authors, Yan Cai.
Tumour Biol, 2015 Oct 21; 37(3). PMID: 26482613
Tim3+ Foxp3 + Treg Cells Are Potent Inhibitors of Effector T Cells and Are Suppressed in Rheumatoid Arthritis.
Huaqiang Sun, Wenwu Gao, +6 authors, Shufeng Li.
Inflammation, 2017 May 10; 40(4). PMID: 28478516
Downregulation of IL-10 secretion by Treg cells in osteoarthritis is associated with a reduction in Tim-3 expression.
Shufeng Li, Jinliang Wan, +7 authors, Wendy Smith.
Biomed Pharmacother, 2016 Apr 06; 79. PMID: 27044824
Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.
Stephen L Hauser, Amit Bar-Or, +19 authors, OPERA I and OPERA II Clinical Investigators.
N Engl J Med, 2016 Dec 22; 376(3). PMID: 28002679
Highly Cited.
Type 1 diabetes immunotherapy using polyclonal regulatory T cells.
Jeffrey A Bluestone, Jane H Buckner, +15 authors, Qizhi Tang.
Sci Transl Med, 2015 Nov 27; 7(315). PMID: 26606968    Free PMC article.
Highly Cited.
Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity.
Marco Romano, Giorgia Fanelli, +2 authors, Giovanna Lombardi.
Front Immunol, 2019 Feb 26; 10. PMID: 30804926    Free PMC article.
Highly Cited. Review.
Chimeric Antigen Receptor (CAR) Treg: A Promising Approach to Inducing Immunological Tolerance.
Qunfang Zhang, Weihui Lu, +4 authors, Zhenhua Dai.
Front Immunol, 2018 Oct 30; 9. PMID: 30369931    Free PMC article.
Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy.
Paula D Bos, George Plitas, +2 authors, Alexander Y Rudensky.
J Exp Med, 2013 Oct 16; 210(11). PMID: 24127486    Free PMC article.
Highly Cited.
Crosstalk between Regulatory T Cells and Tumor-Associated Dendritic Cells Negates Anti-tumor Immunity in Pancreatic Cancer.
Jung-Eun Jang, Cristina H Hajdu, +3 authors, Dafna Bar-Sagi.
Cell Rep, 2017 Jul 21; 20(3). PMID: 28723561    Free PMC article.
Highly Cited.
A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.
Prabhakaran Kumar, Palash Bhattacharya, Bellur S Prabhakar.
J Autoimmun, 2018 Sep 04; 95. PMID: 30174217    Free PMC article.
Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups.
Lawrence P Andrews, Hiroshi Yano, Dario A A Vignali.
Nat Immunol, 2019 Oct 16; 20(11). PMID: 31611702
Immune checkpoint inhibitor myocarditis.
Jayant Raikhelkar, Nir Uriel.
Curr Opin Cardiol, 2019 Mar 30; 34(3). PMID: 30925516
Multiple sclerosis outcomes after cancer immunotherapy.
Catherine R Garcia, Rani Jayswal, +2 authors, John L Villano.
Clin Transl Oncol, 2019 Feb 23; 21(10). PMID: 30788836    Free PMC article.
CNS demyelination and enhanced myelin-reactive responses after ipilimumab treatment.
Yonghao Cao, Alyssa Nylander, +7 authors, David Pitt.
Neurology, 2016 Mar 18; 86(16). PMID: 26984943    Free PMC article.
CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis.
Lisa Ann Gerdes, Kathrin Held, +9 authors, Reinhard Hohlfeld.
Ann Neurol, 2016 Jun 29; 80(2). PMID: 27351142    Free PMC article.
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies.
Yannick Bulliard, Rose Jolicoeur, +6 authors, Jennifer L Brogdon.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897982    Free PMC article.
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.
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.
Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
Frederick Arce Vargas, Andrew J S Furness, +32 authors, Sergio A Quezada.
Cancer Cell, 2018 Mar 27; 33(4). PMID: 29576375    Free PMC article.
Highly Cited.
Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity.
Chien-Chun Steven Pai, Donald M Simons, +22 authors, Lawrence Fong.
J Clin Invest, 2018 Dec 12; 129(1). PMID: 30530991    Free PMC article.
Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody.
Danbee Ha, Atsushi Tanaka, +10 authors, Shimon Sakaguchi.
Proc Natl Acad Sci U S A, 2018 Dec 28; 116(2). PMID: 30587582    Free PMC article.
CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion.
Brian Kavanagh, Shaun O'Brien, +6 authors, Lawrence Fong.
Blood, 2008 Jun 05; 112(4). PMID: 18523152    Free PMC article.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers-Response.
Anu Sharma, Sumit K Subudhi, +5 authors, Padmanee Sharma.
Clin Cancer Res, 2019 Jun 05; 25(11). PMID: 31160495    Free PMC article.
Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation.
Khashayar Esfahani, Tho-Alfakar Al-Aubodah, +9 authors, Wilson H Miller.
Nat Commun, 2019 Oct 19; 10(1). PMID: 31624262    Free PMC article.
Hyperprogressive disease: recognizing a novel pattern to improve patient management.
Stéphane Champiat, Roberto Ferrara, +4 authors, Charles Ferté.
Nat Rev Clin Oncol, 2018 Oct 27; 15(12). PMID: 30361681
Highly Cited. Review.
Decline of programmed death-1-positive circulating T regulatory cells predicts more favourable clinical outcome of patients with melanoma under immune checkpoint blockade.
T Gambichler, U Schröter, +3 authors, J C Becker.
Br J Dermatol, 2019 Jul 31; 182(5). PMID: 31361026
Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4.
Hans Christian Probst, Kathy McCoy, +2 authors, Maries van den Broek.
Nat Immunol, 2005 Feb 03; 6(3). PMID: 15685176
Highly Cited.
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade.
Michael A Postow, Robert Sidlow, Matthew D Hellmann.
N Engl J Med, 2018 Jan 11; 378(2). PMID: 29320654
Highly Cited. Review.
PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells.
Hyo Jin Park, Joon Seok Park, +8 authors, Sang-Jun Ha.
J Immunol, 2015 May 03; 194(12). PMID: 25934860
Highly Cited.
Immune checkpoint inhibitors in cancer therapy: a focus on T-regulatory cells.
Varun Sasidharan Nair, Eyad Elkord.
Immunol Cell Biol, 2018 Jan 24; 96(1). PMID: 29359507
Highly Cited. Review.
Granzyme B-expressing treg cells are enriched in colorectal cancer and present the potential to eliminate autologous T conventional cells.
Bing Sun, Mingtao Liu, Meng Cui, Tao Li.
Immunol Lett, 2019 Nov 02; 217. PMID: 31669380
Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata.
Emeline Castela, Florence Le Duff, +5 authors, Thierry Passeron.
JAMA Dermatol, 2014 May 30; 150(7). PMID: 24872229
Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.
John A Todd, Marina Evangelou, +35 authors, Frank Waldron-Lynch.
PLoS Med, 2016 Oct 12; 13(10). PMID: 27727279    Free PMC article.
Highly Cited.
IL-2/CD25: A Long-Acting Fusion Protein That Promotes Immune Tolerance by Selectively Targeting the IL-2 Receptor on Regulatory T Cells.
Natasha C Ward, Aixin Yu, +11 authors, Thomas R Malek.
J Immunol, 2018 Oct 05; 201(9). PMID: 30282751    Free PMC article.
Interleukin-2 activity can be fine tuned with engineered receptor signaling clamps.
Suman Mitra, Aaron M Ring, +15 authors, Warren J Leonard.
Immunity, 2015 May 21; 42(5). PMID: 25992859    Free PMC article.
Human regulatory T cells lack the cyclophosphamide-extruding transporter ABCB1 and are more susceptible to cyclophosphamide-induced apoptosis.
Sarah Dimeloe, Corina Frick, +6 authors, Christoph Hess.
Eur J Immunol, 2014 Sep 25; 44(12). PMID: 25251877
Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients.
François Ghiringhelli, Cedric Menard, +7 authors, Bruno Chauffert.
Cancer Immunol Immunother, 2006 Sep 09; 56(5). PMID: 16960692
Highly Cited.
Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide.
Yasuhide Motoyoshi, Kazuhisa Kaminoda, +5 authors, Katsumi Eguchi.
Oncol Rep, 2006 Jun 21; 16(1). PMID: 16786137
Diphtheria toxin-based recombinant murine IL-2 fusion toxin for depleting murine regulatory T cells in vivo.
Min Wei, Jose Marino, +8 authors, Zhirui Wang.
Protein Eng Des Sel, 2014 Aug 26; 27(9). PMID: 25147093
Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy.
Kazuhide Sato, Noriko Sato, +5 authors, Hisataka Kobayashi.
Sci Transl Med, 2016 Aug 19; 8(352). PMID: 27535621    Free PMC article.
Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans.
Daisuke Sugiyama, Hiroyoshi Nishikawa, +10 authors, Shimon Sakaguchi.
Proc Natl Acad Sci U S A, 2013 Oct 16; 110(44). PMID: 24127572    Free PMC article.
Highly Cited.
Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia.
Hiroshi Ureshino, Takero Shindo, +15 authors, Shinya Kimura.
Cancer Immunol Res, 2016 May 25; 4(8). PMID: 27215229
The PI3K Pathway in Human Disease.
David A Fruman, Honyin Chiu, +3 authors, Robert T Abraham.
Cell, 2017 Aug 13; 170(4). PMID: 28802037    Free PMC article.
Highly Cited. Review.
Turning off AKT: PHLPP as a drug target.
Alexandra C Newton, Lloyd C Trotman.
Annu Rev Pharmacol Toxicol, 2014 Jan 08; 54. PMID: 24392697    Free PMC article.
Highly Cited. Review.
Cutting edge: PHLPP regulates the development, function, and molecular signaling pathways of regulatory T cells.
Scott J Patterson, Jonathan M Han, +5 authors, Megan K Levings.
J Immunol, 2011 Apr 19; 186(10). PMID: 21498666    Free PMC article.
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.
The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.
Greg M Delgoffe, Thomas P Kole, +6 authors, Jonathan D Powell.
Immunity, 2009 Jun 23; 30(6). PMID: 19538929    Free PMC article.
Highly Cited.
Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity.
Chong T Luo, Will Liao, +2 authors, Ming O Li.
Nature, 2016 Jan 21; 529(7587). PMID: 26789248    Free PMC article.
Highly Cited.
Treatment with rapamycin can restore regulatory T-cell function in IPEX patients.
Laura Passerini, Federica Barzaghi, +20 authors, Rosa Bacchetta.
J Allergy Clin Immunol, 2019 Dec 25; 145(4). PMID: 31874182
A function for interleukin 2 in Foxp3-expressing regulatory T cells.
Jason D Fontenot, Jeffrey P Rasmussen, Marc A Gavin, Alexander Y Rudensky.
Nat Immunol, 2005 Oct 18; 6(11). PMID: 16227984
Highly Cited.
Interleukin 2 signaling is required for CD4(+) regulatory T cell function.
Gláucia C Furtado, Maria A Curotto de Lafaille, Nino Kutchukhidze, Juan J Lafaille.
J Exp Med, 2002 Sep 18; 196(6). PMID: 12235217    Free PMC article.
Highly Cited.
CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2.
Thomas R Malek, Aixin Yu, +2 authors, Lin Kong.
Immunity, 2002 Aug 28; 17(2). PMID: 12196288
Highly Cited.
An essential role for the IL-2 receptor in Treg cell function.
Takatoshi Chinen, Arun K Kannan, +7 authors, Alexander Y Rudensky.
Nat Immunol, 2016 Oct 21; 17(11). PMID: 27595233    Free PMC article.
Highly Cited.
Differential Roles of IL-2 Signaling in Developing versus Mature Tregs.
Martin Y Fan, Jun Siong Low, +5 authors, Laurence A Turka.
Cell Rep, 2018 Nov 01; 25(5). PMID: 30380412    Free PMC article.
Revisiting IL-2: Biology and therapeutic prospects.
Abul K Abbas, Eleonora Trotta, +2 authors, Jeffrey A Bluestone.
Sci Immunol, 2018 Jul 08; 3(25). PMID: 29980618
Highly Cited. Review.
The molecular basis of JAK/STAT inhibition by SOCS1.
Nicholas P D Liau, Artem Laktyushin, +7 authors, Jeffrey J Babon.
Nat Commun, 2018 Apr 21; 9(1). PMID: 29674694    Free PMC article.
Highly Cited.
CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes.
Amy A Caudy, Sreelatha T Reddy, +2 authors, James W Verbsky.
J Allergy Clin Immunol, 2007 Jan 02; 119(2). PMID: 17196245
Highly Cited.
Cutting edge: Decreased accumulation and regulatory function of CD4+ CD25(high) T cells in human STAT5b deficiency.
Aileen C Cohen, Kari C Nadeau, +9 authors, David B Lewis.
J Immunol, 2006 Aug 22; 177(5). PMID: 16920911
Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity.
Kevin Goudy, Didem Aydin, +16 authors, Rosa Bacchetta.
Clin Immunol, 2013 Feb 19; 146(3). PMID: 23416241    Free PMC article.
Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor.
N Sharfe, H K Dadi, M Shahar, C M Roifman.
Proc Natl Acad Sci U S A, 1997 Apr 01; 94(7). PMID: 9096364    Free PMC article.
Highly Cited.
Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4+ T Cells.
Anna Śledzińska, Maria Vila de Mucha, +19 authors, Sergio A Quezada.
Immunity, 2020 Jan 12; 52(1). PMID: 31924474    Free PMC article.
The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases.
David Klatzmann, Abul K Abbas.
Nat Rev Immunol, 2015 Apr 18; 15(5). PMID: 25882245
Highly Cited. Review.
A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism.
Eleonora Trotta, Paul H Bessette, +11 authors, Jeffrey A Bluestone.
Nat Med, 2018 Jun 27; 24(7). PMID: 29942088    Free PMC article.
Highly Cited.
Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'.
Aron M Levin, Darren L Bates, +11 authors, K Christopher Garcia.
Nature, 2012 Mar 27; 484(7395). PMID: 22446627    Free PMC article.
Highly Cited.
The stabilization of PD-L1 by the endoplasmic reticulum stress protein GRP78 in triple-negative breast cancer.
Cheng-Wei Chou, Ri-Yao Yang, +7 authors, Mien-Chie Hung.
Am J Cancer Res, 2020 Sep 10; 10(8). PMID: 32905506    Free PMC article.
Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors.
Lorenzo Galluzzi, Juliette Humeau, +2 authors, Guido Kroemer.
Nat Rev Clin Oncol, 2020 Aug 08; 17(12). PMID: 32760014
Adipose Tissue T Regulatory Cells: Implications for Health and Disease.
David Bradley, Dharti Shantaram, Alan Smith, Willa A Hsueh.
Adv Exp Med Biol, 2021 Feb 02; 1278. PMID: 33523447
Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action.
Carlo Pifferi, Roberto Fuentes, Alberto Fernández-Tejada.
Nat Rev Chem, 2021 Feb 02; 5(3). PMID: 33521324    Free PMC article.
Chimeric Antigen Receptor beyond CAR-T Cells.
Vicky Mengfei Qin, Criselle D'Souza, Paul J Neeson, Joe Jiang Zhu.
Cancers (Basel), 2021 Jan 28; 13(3). PMID: 33499101    Free PMC article.
Immune Privilege: The Microbiome and Uveitis.
Christine Mölzer, Jarmila Heissigerova, +2 authors, John V Forrester.
Front Immunol, 2021 Feb 12; 11. PMID: 33569055    Free PMC article.
Editorial: Control of Regulatory T Cell Stability, Plasticity, and Function in Health and Disease.
Silvia Piconese, Lucy S K Walker, Margarita Dominguez-Villar.
Front Immunol, 2021 Feb 16; 11. PMID: 33584690    Free PMC article.
Tissue Treg Secretomes and Transcription Factors Shared With Stem Cells Contribute to a Treg Niche to Maintain Treg-Ness With 80% Innate Immune Pathways, and Functions of Immunosuppression and Tissue Repair.
Ruijing Zhang, Keman Xu, +16 authors, Xiaofeng Yang.
Front Immunol, 2021 Feb 23; 11. PMID: 33613572    Free PMC article.
Lipid signalling enforces functional specialization of Treg cells in tumours.
Seon Ah Lim, Jun Wei, +9 authors, Hongbo Chi.
Nature, 2021 Feb 26; 591(7849). PMID: 33627871    Free PMC article.
The role of immune-mediated alterations and disorders in ALS disease.
João Rodrigues Lima-Junior, David Sulzer, Cecilia S Lindestam Arlehamn, Alessandro Sette.
Hum Immunol, 2021 Feb 16; 82(3). PMID: 33583639    Free PMC article.
The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity.
Yun-Shiuan Olivia Hsu, Kun-Lin Lu, +8 authors, Chun-Bing Chen.
Front Immunol, 2021 Mar 16; 12. PMID: 33717075    Free PMC article.
Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity.
Muhua Huang, Jingcheng Dong.
J Immunol Res, 2021 Mar 23; 2021. PMID: 33748292    Free PMC article.
Role of Myeloid Cells in Oncolytic Reovirus-Based Cancer Therapy.
Vishnupriyan Kumar, Michael A Giacomantonio, Shashi Gujar.
Viruses, 2021 May 01; 13(4). PMID: 33920168    Free PMC article.
Antigen-Specific Regulatory T Cell Therapy in Autoimmune Diseases and Transplantation.
Claudia Selck, Margarita Dominguez-Villar.
Front Immunol, 2021 Jun 01; 12. PMID: 34054826    Free PMC article.
Canonical Secretomes, Innate Immune Caspase-1-, 4/11-Gasdermin D Non-Canonical Secretomes and Exosomes May Contribute to Maintain Treg-Ness for Treg Immunosuppression, Tissue Repair and Modulate Anti-Tumor Immunity via ROS Pathways.
Dong Ni, TingTing Tang, +14 authors, Xiaofeng Yang.
Front Immunol, 2021 Jun 05; 12. PMID: 34084175    Free PMC article.
Influence of immunomodulatory drugs on the gut microbiota.
Inessa Cohen, William E Ruff, Erin E Longbrake.
Transl Res, 2021 Jan 31; 233. PMID: 33515779    Free PMC article.
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells.
Alejandro J Cagnoni, María Laura Giribaldi, +8 authors, Gabriel A Rabinovich.
Proc Natl Acad Sci U S A, 2021 May 20; 118(21). PMID: 34006646    Free PMC article.
Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma.
Vera Bauer, Fatima Ahmetlić, +3 authors, Ralph Mocikat.
Transl Oncol, 2021 Jul 07; 14(9). PMID: 34229208    Free PMC article.
The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis.
Won-Ju Kim, Gil-Ran Kim, Hyun-Jung Cho, Je-Min Choi.
Pharmaceutics, 2021 Aug 29; 13(8). PMID: 34452095    Free PMC article.
The Multifaceted Role of Regulatory T Cells in Breast Cancer.
Kevin Kos, Karin E de Visser.
Annu Rev Cancer Biol, 2021 Oct 12; 5. PMID: 34632244    Free PMC article.
The kinase PDK1 regulates regulatory T cell survival via controlling redox homeostasis.
Peiran Feng, Quanli Yang, +9 authors, Meixiang Yang.
Theranostics, 2021 Oct 15; 11(19). PMID: 34646383    Free PMC article.
IL-35 promotes CD4+Foxp3+ Tregs and inhibits atherosclerosis via maintaining CCR5-amplified Treg-suppressive mechanisms.
Ying Shao, William Y Yang, +9 authors, Xiaofeng Yang.
JCI Insight, 2021 Oct 09; 6(19). PMID: 34622804    Free PMC article.
T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies.
Josephina A Jansen, Antonio Omuro, Liliana E Lucca.
Curr Opin Neurol, 2021 Sep 28; 34(6). PMID: 34569985    Free PMC article.
Recent Development of Ruminant Vaccine Against Viral Diseases.
Sk Mohiuddin Choudhury, XuSheng Ma, +2 authors, HaiXue Zheng.
Front Vet Sci, 2021 Nov 23; 8. PMID: 34805327    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.
Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression.
Inga Hansine Rye, Kanutte Huse, +9 authors, Hege G Russnes.
Mol Oncol, 2021 Jun 25; 16(1). PMID: 34165864    Free PMC article.
Cannabinoids induce functional Tregs by promoting tolerogenic DCs via autophagy and metabolic reprograming.
Alba Angelina, Mario Pérez-Diego, +6 authors, Oscar Palomares.
Mucosal Immunol, 2021 Sep 23; 15(1). PMID: 34548620    Free PMC article.
GIT1 is an untolerized autoantigen involved in immunologic disturbance of spermatogenesis.
Kenta Nagahori, Miyuki Kuramasu, +5 authors, Masahiro Itoh.
Histochem Cell Biol, 2022 Jan 24; 157(3). PMID: 35066604
Histone Acetylation Regulator-Mediated Acetylation Patterns Define Tumor Malignant Pathways and Tumor Microenvironment in Hepatocellular Carcinoma.
Yuyan Xu, Wei Liao, +2 authors, Mingxin Pan.
Front Immunol, 2022 Feb 12; 13. PMID: 35145517    Free PMC article.
Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells.
Beatriz Lozano-Ruiz, Amalia Tzoumpa, +9 authors, José M González-Navajas.
Int J Mol Sci, 2022 Feb 27; 23(4). PMID: 35216346    Free PMC article.
Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?
Yu-Lei Gao, Ying Yao, +8 authors, Yan-Fen Chai.
Front Immunol, 2022 Mar 15; 13. PMID: 35281010    Free PMC article.
Regulatory T Cells in Autoimmune Vasculitis.
Ke Jin, Simon Parreau, +4 authors, Cornelia M Weyand.
Front Immunol, 2022 Mar 18; 13. PMID: 35296082    Free PMC article.
The Epstein-Barr Virus Hacks Immune Checkpoints: Evidence and Consequences for Lymphoproliferative Disorders and Cancers.
Alison Felipe Bordini Biggi, Deilson Elgui de Oliveira.
Biomolecules, 2022 Mar 26; 12(3). PMID: 35327589    Free PMC article.
4-1BBL-containing leukemic extracellular vesicles promote immunosuppressive effector regulatory T cells.
Julian Swatler, Laura Turos-Korgul, +16 authors, Katarzyna Piwocka.
Blood Adv, 2022 Feb 08; 6(6). PMID: 35130345    Free PMC article.
TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy.
Eugene Y Chiang, Ira Mellman.
J Immunother Cancer, 2022 Apr 06; 10(4). PMID: 35379739    Free PMC article.
Gaussian graphical model-based heterogeneity analysis via penalized fusion.
Mingyang Ren, Sanguo Zhang, Qingzhao Zhang, Shuangge Ma.
Biometrics, 2021 Jan 28;. PMID: 33501648    Free PMC article.
Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity.
Zhongyi Jiang, Haitao Zhu, +4 authors, Futian Du.
MedComm (2020), 2022 Apr 28; 3(2). PMID: 35474948    Free PMC article.
Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets.
Yan Tie, Fan Tang, Yu-Quan Wei, Xia-Wei Wei.
J Hematol Oncol, 2022 May 19; 15(1). PMID: 35585567    Free PMC article.
The Association between Regulatory T Cell Subpopulations and Severe Pneumonia Post Renal Transplantation.
Quan Zhuang, Haozheng Cai, +4 authors, Yingzi Ming.
J Immunol Res, 2022 Apr 20; 2022. PMID: 35437510    Free PMC article.