Journal Article
. 2006 Sep; 177(7):4376-83.
doi: 10.4049/jimmunol.177.7.4376.

Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo

Simon Read 1 Rebecca Greenwald  Ana Izcue  Nicholas Robinson  Didier Mandelbrot  Loise Francisco  Arlene H Sharpe  Fiona Powrie  
Affiliations
  • PMID: 16982872
  •     62 References
  •     180 citations

Abstract

Naturally occurring CD4+ regulatory T cells (T(R)) that express CD25 and the transcription factor FoxP3 play a key role in immune homeostasis, preventing immune pathological responses to self and foreign Ags. CTLA-4 is expressed by a high percentage of these cells, and is often considered as a marker for T(R) in experimental and clinical analysis. However, it has not yet been proven that CTLA-4 has a direct role in T(R) function. In this study, using a T cell-mediated colitis model, we demonstrate that anti-CTLA-4 mAb treatment inhibits T(R) function in vivo via direct effects on CTLA-4-expressing T(R), and not via hyperactivation of colitogenic effector T cells. Although anti-CTLA-4 mAb treatment completely inhibits T(R) function, it does not reduce T(R) numbers or their homing to the GALT, suggesting the Ab mediates its function by blockade of a signal required for T(R) activity. In contrast to the striking effect of the Ab, CTLA-4-deficient mice can produce functional T(R), suggesting that under some circumstances other immune regulatory mechanisms, including the production of IL-10, are able to compensate for the loss of the CTLA-4-mediated pathway. This study provides direct evidence that CTLA-4 has a specific, nonredundant role in the function of normal T(R). This role has to be taken into account when targeting CTLA-4 for therapeutic purposes, as such a strategy will not only boost effector T cell responses, but might also break T(R)-mediated self-tolerance.

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1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3.
Louisa E Jeffery, Fiona Burke, +7 authors, David M Sansom.
J Immunol, 2009 Oct 22; 183(9). PMID: 19843932    Free PMC article.
Highly Cited.
FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells.
Anita Schildknecht, Sabine Brauer, +5 authors, Maries van den Broek.
Proc Natl Acad Sci U S A, 2009 Dec 19; 107(1). PMID: 20018763    Free PMC article.
Ex vivo expanded cord blood CD4 T lymphocytes exhibit a distinct expression profile of cytokine-related genes from those of peripheral blood origin.
Yoshitaka Miyagawa, Nobutaka Kiyokawa, +11 authors, Shigeyoshi Fujiwara.
Immunology, 2010 Jan 14; 128(3). PMID: 20067540    Free PMC article.
Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity.
Nitya Jain, Hai Nguyen, Cynthia Chambers, Joonsoo Kang.
Proc Natl Acad Sci U S A, 2010 Jan 19; 107(4). PMID: 20080649    Free PMC article.
Harnessing regulatory T cells to suppress asthma: from potential to therapy.
Alison N Thorburn, Philip M Hansbro.
Am J Respir Cell Mol Biol, 2010 Jan 26; 43(5). PMID: 20097830    Free PMC article.
Review.
CD4(+)CD25(+) T regulatory cells inhibit CD8(+) IFN-gamma production during acute and chronic FIV infection utilizing a membrane TGF-beta-dependent mechanism.
Jonathan E Fogle, Angela M Mexas, Wayne A Tompkins, Mary B Tompkins.
AIDS Res Hum Retroviruses, 2010 Feb 17; 26(2). PMID: 20156102    Free PMC article.
Regulatory T cells: immune suppression and beyond.
Yisong Y Wan.
Cell Mol Immunol, 2010 Apr 13; 7(3). PMID: 20383175    Free PMC article.
Review.
HIV-specific TGF-beta-positive CD4+ T cells do not express regulatory surface markers and are regulated by CTLA-4.
Mohamed Elrefaei, Candace M Burke, +4 authors, Huyen Cao.
AIDS Res Hum Retroviruses, 2010 May 04; 26(3). PMID: 20433405    Free PMC article.
Modulation of CTLA-4 and GITR for cancer immunotherapy.
Francesca Avogadri, Jianda Yuan, +2 authors, Jedd D Wolchok.
Curr Top Microbiol Immunol, 2010 Jun 22; 344. PMID: 20563707    Free PMC article.
Review.
CTLA-4 blockade following relapse of malignancy after allogeneic stem cell transplantation is associated with T cell activation but not with increased levels of T regulatory cells.
Jiehua Zhou, Asad Bashey, +9 authors, Edward D Ball.
Biol Blood Marrow Transplant, 2010 Aug 18; 17(5). PMID: 20713164    Free PMC article.
Natural regulatory T cells in autoimmunity.
Elaine V Lourenço, Antonio La Cava.
Autoimmunity, 2010 Nov 26; 44(1). PMID: 21091291    Free PMC article.
Review.
Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance.
Virginia A Pedicord, Welby Montalvo, Ingrid M Leiner, James P Allison.
Proc Natl Acad Sci U S A, 2010 Dec 22; 108(1). PMID: 21173239    Free PMC article.
Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism.
Maria E Moreno-Fernandez, Cesar Mauricio Rueda, Laura K Rusie, Claire A Chougnet.
Blood, 2011 Mar 26; 117(20). PMID: 21436067    Free PMC article.
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
Omar S Qureshi, Yong Zheng, +12 authors, David M Sansom.
Science, 2011 Apr 09; 332(6029). PMID: 21474713    Free PMC article.
Highly Cited.
Role of defective autophagia and the intestinal flora in Crohn disease.
Anouk Regeling, Rajesh Somasundaram, +3 authors, Maikel P Peppelenbosch.
Self Nonself, 2011 Apr 14; 1(4). PMID: 21487507    Free PMC article.
Review.
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.
The soluble CTLA-4 splice variant protects from type 1 diabetes and potentiates regulatory T-cell function.
Kay D Gerold, Peilin Zheng, +3 authors, Stephan Kissler.
Diabetes, 2011 May 24; 60(7). PMID: 21602513    Free PMC article.
Resolving the identity myth: key markers of functional CD4+FoxP3+ regulatory T cells.
Xin Chen, Joost J Oppenheim.
Int Immunopharmacol, 2011 Jun 04; 11(10). PMID: 21635972    Free PMC article.
Review.
T regulatory cells are markers of disease activity in multiple sclerosis patients.
Dacia Dalla Libera, Diletta Di Mitri, +12 authors, Roberto Furlan.
PLoS One, 2011 Jul 07; 6(6). PMID: 21731726    Free PMC article.
Immuno-therapy with anti-CTLA4 antibodies in tolerized and non-tolerized mouse tumor models.
Jonas Persson, Ines Beyer, +4 authors, André Lieber.
PLoS One, 2011 Jul 23; 6(7). PMID: 21779410    Free PMC article.
Regulatory T cells selectively control CD8+ T cell effector pool size via IL-2 restriction.
Wolfgang Kastenmuller, Georg Gasteiger, +5 authors, Ronald N Germain.
J Immunol, 2011 Aug 19; 187(6). PMID: 21849683    Free PMC article.
Identification of a unique double-negative regulatory T-cell population.
Byung O Lee, Joyce E Jones, +5 authors, David R Milich.
Immunology, 2011 Nov 03; 134(4). PMID: 22044159    Free PMC article.
Cholera-like enterotoxins and Regulatory T cells.
Christelle Basset, Fatou Thiam, +3 authors, Evelyne Kohli.
Toxins (Basel), 2010 Jul 01; 2(7). PMID: 22069660    Free PMC article.
Review.
Induced Foxp3(+) regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases?
Qin Lan, Huimin Fan, +3 authors, Song Guo Zheng.
J Mol Cell Biol, 2011 Nov 24; 4(1). PMID: 22107826    Free PMC article.
Review.
The dendritic cell-regulatory T lymphocyte crosstalk contributes to tumor-induced tolerance.
Nona Janikashvili, Bernard Bonnotte, Emmanuel Katsanis, Nicolas Larmonier.
Clin Dev Immunol, 2011 Nov 24; 2011. PMID: 22110524    Free PMC article.
Review.
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses.
Lucy S K Walker, David M Sansom.
Nat Rev Immunol, 2011 Nov 26; 11(12). PMID: 22116087
Highly Cited.
Overexpression of the Ctla-4 isoform lacking exons 2 and 3 causes autoimmunity.
Sue M Liu, Andrew P R Sutherland, +7 authors, Vijay K Kuchroo.
J Immunol, 2011 Nov 30; 188(1). PMID: 22124121    Free PMC article.
Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue.
Jeffrey Pido-Lopez, William W Kwok, +2 authors, Neil A Williams.
PLoS Pathog, 2011 Dec 07; 7(12). PMID: 22144893    Free PMC article.
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.
Recipient CTLA-4*CT60-AA genotype is a prognostic factor for acute graft-versus-host disease in hematopoietic stem cell transplantation for thalassemia.
Sandro Orrù, Nicola Orrù, +10 authors, Giorgio La Nasa.
Hum Immunol, 2012 Jan 17; 73(3). PMID: 22245568    Free PMC article.
A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity by maintenance of regulatory T cells via GITR ligand.
Avijit Ray, Sreemanti Basu, +2 authors, Bonnie N Dittel.
J Immunol, 2012 Mar 01; 188(7). PMID: 22368274    Free PMC article.
Highly Cited.
Unmasking the immune recognition of prostate cancer with CTLA4 blockade.
Serena S Kwek, Edward Cha, Lawrence Fong.
Nat Rev Cancer, 2012 Mar 02; 12(4). PMID: 22378189    Free PMC article.
Review.
Selective expansion of allogeneic regulatory T cells by hepatic stellate cells: role of endotoxin and implications for allograft tolerance.
Anil Dangi, Tina L Sumpter, +7 authors, Chandrashekhar R Gandhi.
J Immunol, 2012 Mar 20; 188(8). PMID: 22427640    Free PMC article.
Pathogenic and regulatory roles for B cells in experimental autoimmune encephalomyelitis.
Monica K Mann, Avijit Ray, +2 authors, Bonnie N Dittel.
Autoimmunity, 2012 Mar 27; 45(5). PMID: 22443691    Free PMC article.
Review.
Targeting costimulatory molecules to improve antitumor immunity.
Daria Capece, Daniela Verzella, +2 authors, Edoardo Alesse.
J Biomed Biotechnol, 2012 Apr 14; 2012. PMID: 22500111    Free PMC article.
Review.
Molecular mechanisms of treg-mediated T cell suppression.
Angelika Schmidt, Nina Oberle, Peter H Krammer.
Front Immunol, 2012 May 09; 3. PMID: 22566933    Free PMC article.
Highly Cited.
Inhibitory receptors are expressed by Trypanosoma cruzi-specific effector T cells and in hearts of subjects with chronic Chagas disease.
Rafael J Argüello, María C Albareda, +6 authors, Susana A Laucella.
PLoS One, 2012 May 11; 7(5). PMID: 22574131    Free PMC article.
Boosting regulatory T cell function by CD4 stimulation enters the clinic.
Christian Becker, Tobias Bopp, Helmut Jonuleit.
Front Immunol, 2012 Jun 22; 3. PMID: 22719741    Free PMC article.
Immune checkpoints in central nervous system autoimmunity.
Nicole Joller, Anneli Peters, Ana C Anderson, Vijay K Kuchroo.
Immunol Rev, 2012 Jun 26; 248(1). PMID: 22725958    Free PMC article.
Review.
Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells.
Chun Jing Wang, Rupert Kenefeck, +6 authors, Lucy S K Walker.
J Immunol, 2012 Jul 04; 189(3). PMID: 22753931    Free PMC article.
Innate immunity, decidual cells, and preeclampsia.
Chang-Ching Yeh, Kuan-Chong Chao, S Joseph Huang.
Reprod Sci, 2012 Jul 21; 20(4). PMID: 22814099    Free PMC article.
Review.
Immunoregulatory molecules are master regulators of inflammation during the immune response.
Hortensia de la Fuente, Danay Cibrián, Francisco Sánchez-Madrid.
FEBS Lett, 2012 Jul 24; 586(18). PMID: 22819828    Free PMC article.
Review.
CTLA-4 promotes Foxp3 induction and regulatory T cell accumulation in the intestinal lamina propria.
M J Barnes, T Griseri, +3 authors, A Izcue.
Mucosal Immunol, 2012 Aug 23; 6(2). PMID: 22910217    Free PMC article.
Expansion in CD39⁺ CD4⁺ immunoregulatory t cells and rarity of Th17 cells in HTLV-1 infected patients is associated with neurological complications.
Fabio E Leal, Lishomwa C Ndhlovu, +8 authors, Esper G Kallas.
PLoS Negl Trop Dis, 2013 Feb 15; 7(2). PMID: 23409198    Free PMC article.
Allergic conjunctivitis renders CD4(+) T cells resistant to t regulatory cells and exacerbates corneal allograft rejection.
N J Reyes, P W Chen, J Y Niederkorn.
Am J Transplant, 2013 Mar 16; 13(5). PMID: 23489547    Free PMC article.
Ribavirin Does Not Impair the Suppressive Activity of Foxp3(+)CD4(+)CD25(+) Regulatory T Cells.
Jeewon Lee, Yoon Seok Choi, Eui-Cheol Shin.
Immune Netw, 2013 Apr 06; 13(1). PMID: 23559897    Free PMC article.
At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy.
Andrew M Intlekofer, Craig B Thompson.
J Leukoc Biol, 2013 Apr 30; 94(1). PMID: 23625198    Free PMC article.
Highly Cited. Review.
T-cell tolerance in cancer.
Roza Nurieva, Junmei Wang, Anupama Sahoo.
Immunotherapy, 2013 May 04; 5(5). PMID: 23638746    Free PMC article.
Review.
Induced and natural regulatory T cells in the development of inflammatory bowel disease.
Christopher G Mayne, Calvin B Williams.
Inflamm Bowel Dis, 2013 May 10; 19(8). PMID: 23656897    Free PMC article.
Review.
Thymic versus induced regulatory T cells - who regulates the regulators?
Giovanni Antonio Maria Povoleri, Cristiano Scottà, +3 authors, Behdad Afzali.
Front Immunol, 2013 Jul 03; 4. PMID: 23818888    Free PMC article.
Treg and CTLA-4: two intertwining pathways to immune tolerance.
Lucy S K Walker.
J Autoimmun, 2013 Jul 16; 45. PMID: 23849743    Free PMC article.
Highly Cited. Review.
Regulatory T cells vs Th17: differentiation of Th17 versus Treg, are the mutually exclusive?
Song Guo Zheng.
Am J Clin Exp Immunol, 2013 Jul 26; 2(1). PMID: 23885327    Free PMC article.
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.
CTLA4Ig inhibits effector T cells through regulatory T cells and TGF-β.
Christine M Deppong, Traci L Bricker, +3 authors, Jonathan M Green.
J Immunol, 2013 Aug 21; 191(6). PMID: 23956428    Free PMC article.
Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.
Jeffrey S Weber, Ragini Reiney Kudchadkar, +11 authors, Y Ann Chen.
J Clin Oncol, 2013 Oct 23; 31(34). PMID: 24145345    Free PMC article.
Highly Cited.
Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management.
Ahmad Tarhini.
Scientifica (Cairo), 2013 Nov 28; 2013. PMID: 24278787    Free PMC article.
Highly Cited. Review.
CD4+ primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells.
Cecilia Fernandez-Ponce, Margarita Dominguez-Villar, Enrique Aguado, Francisco Garcia-Cozar.
PLoS One, 2014 Jan 28; 9(1). PMID: 24465502    Free PMC article.
Investigation of soluble and transmembrane CTLA-4 isoforms in serum and microvesicles.
Laura Esposito, Kara M D Hunter, +12 authors, Linda S Wicker.
J Immunol, 2014 Jun 15; 193(2). PMID: 24928993    Free PMC article.
IFNαR signaling in effector but not regulatory T cells is required for immune dysregulation during type I IFN-dependent inflammatory disease.
Shivani Srivastava, Lisa K Koch, Daniel J Campbell.
J Immunol, 2014 Aug 06; 193(6). PMID: 25092894    Free PMC article.
Tr-1-like CD4+CD25-CD127-/lowFOXP3- cells are the main source of interleukin 10 in patients with cutaneous leishmaniasis due to Leishmania braziliensis.
Diego L Costa, Tiago M Cardoso, +4 authors, João S Silva.
J Infect Dis, 2014 Aug 21; 211(5). PMID: 25139022    Free PMC article.
Amniotic membrane mesenchymal cells-derived factors skew T cell polarization toward Treg and downregulate Th1 and Th17 cells subsets.
Stefano Pianta, Patrizia Bonassi Signoroni, +4 authors, Ornella Parolini.
Stem Cell Rev Rep, 2014 Oct 29; 11(3). PMID: 25348066    Free PMC article.
Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming.
Melanie P Matheu, Shivashankar Othy, +7 authors, Michael D Cahalan.
Nat Commun, 2015 Feb 06; 6. PMID: 25653051    Free PMC article.
Immunotherapy in Cancer: A Combat between Tumors and the Immune System; You Win Some, You Lose Some.
Florencia Paula Madorsky Rowdo, Antonela Baron, Mariela Urrutia, José Mordoh.
Front Immunol, 2015 Apr 11; 6. PMID: 25859247    Free PMC article.
Review.
In-situ tumor vaccination: Bringing the fight to the tumor.
Robert H Pierce, Jean S Campbell, +2 authors, Holbrook E K Kohrt.
Hum Vaccin Immunother, 2015 Jun 10; 11(8). PMID: 26055074    Free PMC article.
Review.
Regulatory immune cells in regulation of intestinal inflammatory response to microbiota.
M Sun, C He, Y Cong, Z Liu.
Mucosal Immunol, 2015 Jun 18; 8(5). PMID: 26080708    Free PMC article.
Highly Cited. Review.
Paradoxical psoriasiform reactions to anti-TNFα drugs are associated with genetic polymorphisms in patients with psoriasis.
T Cabaleiro, R Prieto-Pérez, +5 authors, E Daudén.
Pharmacogenomics J, 2015 Jul 22; 16(4). PMID: 26194362
Different aspects of CD4 T cells that lead to viral clearance or persistence of HCV infection.
Kazushi Sugimoto, Katsuya Shiraki.
Hepatol Int, 2012 Jan 01; 6(1). PMID: 26201340
Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity.
Alison M Paterson, Scott B Lovitch, +9 authors, Arlene H Sharpe.
J Exp Med, 2015 Sep 16; 212(10). PMID: 26371185    Free PMC article.
Highly Cited.
Immune checkpoints and immunotherapy for colorectal cancer.
Preet Paul Singh, Piyush K Sharma, Gayathri Krishnan, A Craig Lockhart.
Gastroenterol Rep (Oxf), 2015 Oct 30; 3(4). PMID: 26510455    Free PMC article.
CTLA-4 and Autoimmunity: New Twists in the Tale.
Lucy S K Walker.
Trends Immunol, 2015 Nov 26; 36(12). PMID: 26596798    Free PMC article.
Immune homeostasis enforced by co-localized effector and regulatory T cells.
Zhiduo Liu, Michael Y Gerner, +3 authors, Ronald N Germain.
Nature, 2015 Nov 26; 528(7581). PMID: 26605524    Free PMC article.
Highly Cited.
Disrupted regulatory T cell homeostasis in inflammatory bowel diseases.
Christophe Pedros, Fanny Duguet, Abdelhadi Saoudi, Marianne Chabod.
World J Gastroenterol, 2016 Jan 27; 22(3). PMID: 26811641    Free PMC article.
Review.
Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition.
Joanna Brzostek, Nicholas R J Gascoigne, Vasily Rybakin.
Front Immunol, 2016 Feb 13; 7. PMID: 26870040    Free PMC article.
Review.
Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment.
Stefani Spranger.
Int Immunol, 2016 Mar 19; 28(8). PMID: 26989092    Free PMC article.
Highly Cited. Review.
Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood.
Katrin Klocke, Shimon Sakaguchi, Rikard Holmdahl, Kajsa Wing.
Proc Natl Acad Sci U S A, 2016 Apr 14; 113(17). PMID: 27071130    Free PMC article.
Highly Cited.
Tumor Progression Locus 2 (Tpl2) Activates the Mammalian Target of Rapamycin (mTOR) Pathway, Inhibits Forkhead Box P3 (FoxP3) Expression, and Limits Regulatory T Cell (Treg) Immunosuppressive Functions.
Xin Li, Nicole V Acuff, +4 authors, Wendy T Watford.
J Biol Chem, 2016 Jun 05; 291(32). PMID: 27261457    Free PMC article.
Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide as First-Line Therapy for Extensive-Stage SCLC.
Edurne Arriola, Matthew Wheater, +13 authors, Christian Ottensmeier.
J Thorac Oncol, 2016 Jun 15; 11(9). PMID: 27296105    Free PMC article.
CTLA-4 Limits Anti-CD20-Mediated Tumor Regression.
Zhenhua Ren, Jingya Guo, +7 authors, Yang-Xin Fu.
Clin Cancer Res, 2016 Jun 30; 23(1). PMID: 27354469    Free PMC article.
Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis.
Edurne Arriola, Matthew Wheater, +2 authors, Christian Ottensmeier.
Oncoimmunology, 2016 Oct 21; 5(9). PMID: 27757302    Free PMC article.
Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them?
Anabelle Visperas, Dario A A Vignali.
J Immunol, 2016 Nov 07; 197(10). PMID: 27815439    Free PMC article.
Review.
Soluble CD200 Correlates With Interleukin-6 Levels in Sera of COPD Patients: Potential Implication of the CD200/CD200R Axis in the Disease Course.
Priya Sakthivel, Angele Breithaupt, +6 authors, Dunja Bruder.
Lung, 2016 Nov 20; 195(1). PMID: 27864635
Immune modulation of CD4+CD25+ regulatory T cells by zoledronic acid.
Hsien Liu, Shih-Han Wang, +3 authors, Tsun-Mei Lin.
BMC Immunol, 2016 Nov 27; 17(1). PMID: 27887569    Free PMC article.
Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora?
Franck Carbonnel, Emilie Soularue, +4 authors, Caroline Robert.
Semin Immunopathol, 2017 Jan 18; 39(3). PMID: 28093620
Review.
Co-inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma.
Liliana E Lucca, David A Hafler.
Immunol Rev, 2017 Mar 05; 276(1). PMID: 28258696    Free PMC article.
Review.
Methylation of FOXP3 TSDR Underlies the Impaired Suppressive Function of Tregs from Long-term Belatacept-Treated Kidney Transplant Patients.
Evelyn Katy Alvarez Salazar, Arimelek Cortés-Hernández, +14 authors, Gloria Soldevila.
Front Immunol, 2017 Mar 21; 8. PMID: 28316600    Free PMC article.
An Anti-Programmed Death-1 Antibody (αPD-1) Fusion Protein That Self-Assembles into a Multivalent and Functional αPD-1 Nanoparticle.
Peng Zhao, Djordje Atanackovic, +3 authors, Mingnan Chen.
Mol Pharm, 2017 Mar 28; 14(5). PMID: 28343398    Free PMC article.
Preferential accumulation of regulatory T cells with highly immunosuppressive characteristics in breast tumor microenvironment.
Azharuddin Sajid Syed Khaja, Salman M Toor, +4 authors, Eyad Elkord.
Oncotarget, 2017 Apr 08; 8(20). PMID: 28388539    Free PMC article.
Escherichia coli Heat-Labile Enterotoxin B Limits T Cells Activation by Promoting Immature Dendritic Cells and Enhancing Regulatory T Cell Function.
Alexandre Bignon, Alan P Watt, Michelle A Linterman.
Front Immunol, 2017 May 31; 8. PMID: 28555139    Free PMC article.
Intratumoral FoxP3+Helios+ Regulatory T Cells Upregulating Immunosuppressive Molecules Are Expanded in Human Colorectal Cancer.
Azharuddin Sajid Syed Khaja, Salman M Toor, +2 authors, Eyad Elkord.
Front Immunol, 2017 Jun 13; 8. PMID: 28603527    Free PMC article.
Tremelimumab-Induced Graves Hyperthyroidism.
Earn H Gan, Anna L Mitchell, +2 authors, Petros Perros.
Eur Thyroid J, 2017 Aug 09; 6(3). PMID: 28785544    Free PMC article.
T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma.
Daniele Maggioni, Lorenzo Pignataro, Werner Garavello.
Oncoimmunology, 2017 Aug 16; 6(7). PMID: 28811959    Free PMC article.
Review.
Regulatory T cells in acute and chronic kidney diseases.
Rahul Sharma, Gilbert R Kinsey.
Am J Physiol Renal Physiol, 2017 Sep 08; 314(5). PMID: 28877881    Free PMC article.
Review.
Human regulatory T cells undergo self-inflicted damage via granzyme pathways upon activation.
Esilida Sula Karreci, Siawosh K Eskandari, +18 authors, Jamil Azzi.
JCI Insight, 2017 Nov 03; 2(21). PMID: 29093262    Free PMC article.
The sexist behaviour of immune checkpoint inhibitors in cancer therapy?
Andrea Botticelli, Concetta Elisa Onesti, +15 authors, Paolo Marchetti.
Oncotarget, 2017 Dec 17; 8(59). PMID: 29245905    Free PMC article.
Lentiviral delivery of CTLA-4 shRNA improves the expansion of cytokine-induced killer cells and enhances cytotoxic activity in vitro.
Tao Rui, Xiangdong Cheng, +3 authors, Guoqing Wu.
Oncol Lett, 2018 Feb 06; 15(1). PMID: 29399145    Free PMC article.
Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis.
B L Adler, M K Pezhouh, +15 authors, R A Anders.
J Intern Med, 2018 Feb 22; 283(6). PMID: 29464806    Free PMC article.
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.
Promises and limitations of immune cell-based therapies in neurological disorders.
Xiaoming Hu, Rehana K Leak, +4 authors, Jun Chen.
Nat Rev Neurol, 2018 Jun 22; 14(9). PMID: 29925925    Free PMC article.
Review.
Resistance to Radiotherapy and PD-L1 Blockade Is Mediated by TIM-3 Upregulation and Regulatory T-Cell Infiltration.
Ayman Oweida, Mohammad K Hararah, +14 authors, Sana D Karam.
Clin Cancer Res, 2018 Jul 26; 24(21). PMID: 30042205    Free PMC article.
Highly Cited.
Not All Immune Checkpoints Are Created Equal.
Annika De Sousa Linhares, Judith Leitner, Katharina Grabmeier-Pfistershammer, Peter Steinberger.
Front Immunol, 2018 Sep 21; 9. PMID: 30233564    Free PMC article.
Highly Cited. Review.
Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases.
Jae-Ung Lee, Li-Kyung Kim, Je-Min Choi.
Front Immunol, 2018 Dec 13; 9. PMID: 30538703    Free PMC article.
Review.
Preclinical rationale and clinical efficacy of antiangiogenic therapy and immune checkpoint blockade combination therapy in urogenital tumors.
Ning Zhu, Shanshan Weng, +4 authors, Ying Yuan.
J Cancer Res Clin Oncol, 2019 Oct 17; 145(12). PMID: 31617075
Review.
Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors.
Hajir Ibraheim, Esperanza Perucha, Nick Powell.
Rheumatology (Oxford), 2019 Dec 10; 58(Suppl 7). PMID: 31816081    Free PMC article.
Review.
Toxicity of tumor immune checkpoint inhibitors-more attention should be paid.
Yu Liu, Hao Wang, +3 authors, Caicun Zhou.
Transl Lung Cancer Res, 2020 Feb 06; 8(6). PMID: 32010590    Free PMC article.
Review.
Dissecting the Heterogeneity in T-Cell Mediated Inflammation in IBD.
Irma Tindemans, Maria E Joosse, Janneke N Samsom.
Cells, 2020 Jan 08; 9(1). PMID: 31906479    Free PMC article.
Review.
A QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade.
Oleg Milberg, Chang Gong, +6 authors, Aleksander S Popel.
Sci Rep, 2019 Aug 04; 9(1). PMID: 31375756    Free PMC article.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers.
Anu Sharma, Sumit K Subudhi, +6 authors, Padmanee Sharma.
Clin Cancer Res, 2018 Jul 29; 25(4). PMID: 30054281    Free PMC article.
Highly Cited.
Association among cytotoxic T-lymphocyte antigen 4 gene, rs231775 polymorphism, and recurrent pregnancy loss risk.
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Biosci Rep, 2018 Dec 24; 39(2). PMID: 30578376    Free PMC article.
CTLA-4-mediated transendocytosis of costimulatory molecules primarily targets migratory dendritic cells.
Vitalijs Ovcinnikovs, Ellen M Ross, +9 authors, Lucy S K Walker.
Sci Immunol, 2019 Jun 04; 4(35). PMID: 31152091    Free PMC article.
Genetics of recurrent pregnancy loss among Iranian population.
Meysam Moghbeli.
Mol Genet Genomic Med, 2019 Aug 01; 7(9). PMID: 31364314    Free PMC article.
Review.
Human Memory Th17 Cell Populations Change Into Anti-inflammatory Cells With Regulatory Capacity Upon Exposure to Active Vitamin D.
Wendy Dankers, Nadine Davelaar, +3 authors, Erik Lubberts.
Front Immunol, 2019 Aug 06; 10. PMID: 31379807    Free PMC article.
A guide to cancer immunotherapy: from T cell basic science to clinical practice.
Alex D Waldman, Jill M Fritz, Michael J Lenardo.
Nat Rev Immunol, 2020 May 21; 20(11). PMID: 32433532    Free PMC article.
Review.
Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell-Dependent Mechanisms.
Ciara N Magee, Naoka Murakami, +15 authors, Leonardo V Riella.
Circulation, 2019 Jul 04; 140(10). PMID: 31266349    Free PMC article.
Immunological Targets for Immunotherapy: Inhibitory T Cell Receptors.
Diwakar Davar, Hassane M Zarour.
Methods Mol Biol, 2019 Sep 11; 2055. PMID: 31502146    Free PMC article.
Review.
Targeting immune checkpoints in hematological malignancies.
Basit Salik, Mark J Smyth, Kyohei Nakamura.
J Hematol Oncol, 2020 Aug 14; 13(1). PMID: 32787882    Free PMC article.
Review.
Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.
Lukas Amon, Lukas Hatscher, +2 authors, Christian H K Lehmann.
Pharmaceutics, 2020 Jul 18; 12(7). PMID: 32674488    Free PMC article.
Review.
Scientifically based combination therapies with immuno-oncology checkpoint inhibitors.
Hui Yi Chew, Riccardo Dolcetti, Fiona Simpson.
Br J Clin Pharmacol, 2020 May 07; 86(9). PMID: 32372470    Free PMC article.
Review.
Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials.
Antonino Grassadonia, Isabella Sperduti, +11 authors, Nicola Tinari.
J Clin Med, 2018 Dec 14; 7(12). PMID: 30545122    Free PMC article.
Immunotherapy in Hematologic Malignancies: Emerging Therapies and Novel Approaches.
Ji-Yoon Noh, Huiyun Seo, Jungwoon Lee, Haiyoung Jung.
Int J Mol Sci, 2020 Oct 31; 21(21). PMID: 33121189    Free PMC article.
Review.
Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?
Negar Hosseinkhani, Afshin Derakhshani, +9 authors, Behzad Baradaran.
Int J Mol Sci, 2020 Nov 11; 21(21). PMID: 33167514    Free PMC article.
Review.
Will Next-Generation Immunotherapy Overcome the Intrinsic Diversity and Low Immunogenicity of Sarcomas to Improve Clinical Benefit?
Hui Yi Chew, Victor Chan, Fiona Simpson, Riccardo Dolcetti.
Cancers (Basel), 2020 Nov 20; 12(11). PMID: 33207697    Free PMC article.
Review.
Ipilimumab in prostate cancer.
Nishith Singh, Ravi A Madan, James L Gulley.
Expert Opin Biol Ther, 2012 Dec 26; 13(2). PMID: 23265575    Free PMC article.
Review.
Zoledronic acid blocks the interaction between breast cancer cells and regulatory T-cells.
Hsien Liu, Shih-Han Wang, +2 authors, Tsun-Mei Lin.
BMC Cancer, 2019 Feb 28; 19(1). PMID: 30808421    Free PMC article.
Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types.
Damilola Oyewole-Said, Vanaja Konduri, +3 authors, William K Decker.
Front Immunol, 2021 Jan 02; 11. PMID: 33384695    Free PMC article.
Review.
Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity.
Allan Relecom, Maysaloun Merhi, +4 authors, Said Dermime.
J Exp Clin Cancer Res, 2021 Feb 20; 40(1). PMID: 33602280    Free PMC article.
Review.
Nanobody-based CTLA4 inhibitors for immune checkpoint blockade therapy of canine cancer patients.
Jonathan Marable, Damien Ruiz, +8 authors, Maninder Sandey.
Sci Rep, 2021 Oct 23; 11(1). PMID: 34675296    Free PMC article.
Proteomics as a Complementary Technique to Characterize Bladder Cancer.
Rubén López-Cortés, Sergio Vázquez-Estévez, Javier Álvarez Fernández, Cristina Núñez.
Cancers (Basel), 2021 Nov 14; 13(21). PMID: 34771699    Free PMC article.
Review.
PD-L1 is expressed on human activated naive effector CD4+ T cells. Regulation by dendritic cells and regulatory CD4+ T cells.
Fabienne Mazerolles, Frédéric Rieux-Laucat.
PLoS One, 2021 Nov 19; 16(11). PMID: 34793567    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.
Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.
Somayeh Vafaei, Angelina O Zekiy, +4 authors, Majid Zamani.
Cancer Cell Int, 2022 Jan 05; 22(1). PMID: 34980128    Free PMC article.
Review.
HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study.
Vivek Naranbhai, Mathias Viard, +14 authors, Mary Carrington.
Lancet Oncol, 2021 Dec 14; 23(1). PMID: 34895481    Free PMC article.
SARS-CoV-2 infection causes intestinal cell damage: Role of interferon's imbalance.
Stefany Guimarães Sousa, Antônio Kleiton de Sousa, +4 authors, André Luiz Dos Reis Barbosa.
Cytokine, 2022 Feb 15; 152. PMID: 35158258    Free PMC article.
Review.
Tissue Resident Foxp3+ Regulatory T Cells: Sentinels and Saboteurs in Health and Disease.
Juyeun Lee, Dongkyun Kim, Booki Min.
Front Immunol, 2022 Apr 02; 13. PMID: 35359918    Free PMC article.
Review.
Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
Adel Naimi, Rebar N Mohammed, +11 authors, Ehsan Razeghian.
Cell Commun Signal, 2022 Apr 09; 20(1). PMID: 35392976    Free PMC article.
Review.
Tipping the balance: inhibitory checkpoints in intestinal homeostasis.
Maria E Joosse, Iris Nederlof, Lucy S K Walker, Janneke N Samsom.
Mucosal Immunol, 2018 Dec 01; 12(1). PMID: 30498201
Review.
Immune Checkpoint Inhibitors in Peripheral T-Cell Lymphoma.
Xi Chen, Wanchun Wu, Wenwen Wei, Liqun Zou.
Front Pharmacol, 2022 May 14; 13. PMID: 35559250    Free PMC article.
Review.