Review
. 2007 Oct; 7(11):880-7.
doi: 10.1038/nrc2250.

Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy

Mario P Colombo 1 Silvia Piconese  
Affiliations
  • PMID: 17957190
  •     163 citations

Abstract

Tumour-induced expansion of regulatory T (T(Reg)) cells is an obstacle to successful cancer immunotherapy. The potential benefit of T(Reg)-cell depletion through the interleukin-2 receptor is lost by the concurrent elimination of activated effector lymphocytes and possibly by the de novo induction of T(Reg)-cell replenishment. In theory, the functional inactivation of T(Reg) cells will maintain them at high numbers in tumours and avoid their replenishment from the peripheral lymphocyte pool, which has the capacity to further suppress the effector lymphocyte anti-tumour response.

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Chiara Camisaschi, Viviana Vallacchi, +10 authors, Veronica Huber.
Vaccines (Basel), 2016 Nov 10; 4(4). PMID: 27827921    Free PMC article.
Review.
CCL22-specific T Cells: Modulating the immunosuppressive tumor microenvironment.
Evelina Martinenaite, Shamaila Munir Ahmad, +7 authors, Mads Hald Andersen.
Oncoimmunology, 2016 Dec 22; 5(11). PMID: 27999757    Free PMC article.
Mechanisms by Which B Cells and Regulatory T Cells Influence Development of Murine Organ-Specific Autoimmune Diseases.
Jason S Ellis, Helen Braley-Mullen.
J Clin Med, 2017 Jan 31; 6(2). PMID: 28134752    Free PMC article.
Review.
Mechanism of immune evasion in breast cancer.
Mozhi Wang, Changwang Zhang, +7 authors, Yingying Xu.
Onco Targets Ther, 2017 Mar 30; 10. PMID: 28352189    Free PMC article.
Review.
Immunological effects of vaccines combined with granulocyte colony-stimulating factor on a murine WEHI-3 leukemia model.
Jinqiu Chen, Miling Zhang, +3 authors, Wanggang Zhang.
Oncol Lett, 2017 Apr 30; 13(4). PMID: 28454398    Free PMC article.
Intratumoral depletion of regulatory T cells using CD25-targeted photodynamic therapy in a mouse melanoma model induces antitumoral immune responses.
Dong Sun Oh, Heegon Kim, +4 authors, Heung Kyu Lee.
Oncotarget, 2017 May 26; 8(29). PMID: 28537894    Free PMC article.
Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer.
L D Miteva, N S Stanilov, G М Cirovski, Spaska Angelova Stanilova.
Cancer Microenviron, 2017 Sep 05; 10(1-3). PMID: 28868572    Free PMC article.
Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition.
Xia Liu, Wei Mo, +5 authors, Guangyong Peng.
Nat Commun, 2018 Jan 18; 9(1). PMID: 29339767    Free PMC article.
Tumor Necrosis Factor α and Regulatory T Cells in Oncoimmunology.
Benoît L Salomon, Mathieu Leclerc, +3 authors, José L Cohen.
Front Immunol, 2018 Mar 30; 9. PMID: 29593717    Free PMC article.
Review.
IL-27 gene therapy induces depletion of Tregs and enhances the efficacy of cancer immunotherapy.
Jianmin Zhu, Jin-Qing Liu, +11 authors, Xue-Feng Bai.
JCI Insight, 2018 Apr 06; 3(7). PMID: 29618655    Free PMC article.
Temozolomide for immunomodulation in the treatment of glioblastoma.
Aida Karachi, Farhad Dastmalchi, Duane A Mitchell, Maryam Rahman.
Neuro Oncol, 2018 May 08; 20(12). PMID: 29733389    Free PMC article.
Review.
Preliminary investigation on the abnormal mechanism of CD4+FOXP3+CD25high regulatory T cells in pediatric B-cell acute lymphoblastic leukemia.
Si-Xi Liu, Hai-Rong Xiao, +6 authors, Fei-Qiu Wen.
Exp Ther Med, 2018 Aug 18; 16(2). PMID: 30116392    Free PMC article.
OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis.
Patrizia Nanni, Carla De Giovanni, +7 authors, Pier-Luigi Lollini.
Oncoimmunology, 2018 Sep 18; 7(8). PMID: 30221061    Free PMC article.
A Single-Chain-Based Hexavalent CD27 Agonist Enhances T Cell Activation and Induces Anti-Tumor Immunity.
Meinolf Thiemann, David M Richards, +10 authors, Oliver Hill.
Front Oncol, 2018 Oct 10; 8. PMID: 30298117    Free PMC article.
Exceptional responses with sequential metronomic temozolomide after pembrolizumab failure in patients with metastatic melanoma.
Umang Swami, Varun Monga, +4 authors, Mohammed Milhem.
Melanoma Res, 2019 Mar 05; 29(6). PMID: 30829928    Free PMC article.
Racial Differences in Immunological Landscape Modifiers Contributing to Disparity in Prostate Cancer.
Jeronay King Thomas, Hina Mir, Neeraj Kapur, Shailesh Singh.
Cancers (Basel), 2019 Nov 27; 11(12). PMID: 31769418    Free PMC article.
Review.
Inhibition Mechanism of Indoleamine 2, 3-Dioxygenase 1 (IDO1) by Amidoxime Derivatives and Its Revelation in Drug Design: Comparative Molecular Dynamics Simulations.
Xinyu Liu, Yiwen Zhang, +7 authors, Hubing Shi.
Front Mol Biosci, 2020 Feb 13; 6. PMID: 32047753    Free PMC article.
Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer.
Franziska Eckert, Karin Schilbach, +5 authors, Stephan M Huber.
Front Immunol, 2019 Jan 10; 9. PMID: 30622535    Free PMC article.
Review.
Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity.
Masanori Onda, Kazuto Kobayashi, Ira Pastan.
Proc Natl Acad Sci U S A, 2019 Feb 15; 116(10). PMID: 30760587    Free PMC article.
Critical role of kinase activity of hematopoietic progenitor kinase 1 in anti-tumor immune surveillance.
Jinqi Liu, Joshua Curtin, +19 authors, Luisa Salter-Cid.
PLoS One, 2019 Mar 27; 14(3). PMID: 30913212    Free PMC article.
Resistance Mechanisms and Barriers to Successful Immunotherapy for Treating Glioblastoma.
Jason Adhikaree, Julia Moreno-Vicente, +2 authors, Poulam M Patel.
Cells, 2020 Jan 25; 9(2). PMID: 31973059    Free PMC article.
Review.
Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy.
Kris M Mahadeo, Sajad J Khazal, +31 authors, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network.
Nat Rev Clin Oncol, 2018 Aug 08; 16(1). PMID: 30082906    Free PMC article.
Highly Cited. Review.
Thymic Function Associated With Cancer Development, Relapse, and Antitumor Immunity - A Mini-Review.
Weikan Wang, Rachel Thomas, Olga Sizova, Dong-Ming Su.
Front Immunol, 2020 May 20; 11. PMID: 32425946    Free PMC article.
Review.
Single-Cell Atlas Reveals Complexity of the Immunosuppressive Microenvironment of Initial and Recurrent Glioblastoma.
Weilun Fu, Wenjing Wang, +9 authors, Jizong Zhao.
Front Immunol, 2020 May 28; 11. PMID: 32457755    Free PMC article.
IRF4 instructs effector Treg differentiation and immune suppression in human cancer.
Giorgia Alvisi, Jolanda Brummelman, +18 authors, Enrico Lugli.
J Clin Invest, 2020 Mar 04; 130(6). PMID: 32125291    Free PMC article.
Emerging role of PTEN loss in evasion of the immune response to tumours.
Thiago Vidotto, Camila Morais Melo, +3 authors, Jeremy A Squire.
Br J Cancer, 2020 Apr 25; 122(12). PMID: 32327707    Free PMC article.
Review.
Nanotechnology Strategies To Advance Outcomes in Clinical Cancer Care.
Christopher M Hartshorn, Michelle S Bradbury, +6 authors, Piotr Grodzinski.
ACS Nano, 2017 Dec 20; 12(1). PMID: 29257865    Free PMC article.
Review.
Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects.
Chunxiao Li, Ping Jiang, +2 authors, Junjie Wang.
Mol Cancer, 2020 Jul 19; 19(1). PMID: 32680511    Free PMC article.
Review.
Molecular Heterogeneity and Immunosuppressive Microenvironment in Glioblastoma.
Syreeta DeCordova, Abhishek Shastri, +4 authors, Uday Kishore.
Front Immunol, 2020 Aug 09; 11. PMID: 32765498    Free PMC article.
Review.
Urinary Metals Concentrations and Biomarkers of Autoimmunity among Navajo and Nicaraguan Men.
Madeleine K Scammell, Caryn Sennett, +10 authors, Esther Erdei.
Int J Environ Res Public Health, 2020 Jul 28; 17(15). PMID: 32707746    Free PMC article.
Indoleamine 2, 3-dioxygenase inhibitors in immunochemotherapy of breast cancer: challenges and opportunities.
Nastran Hashemzadeh, Khosro Adibkia, Jaleh Barar.
Bioimpacts, 2019 Feb 23; 9(1). PMID: 30788254    Free PMC article.
Depleting T regulatory cells by targeting intracellular Foxp3 with a TCR mimic antibody.
Tao Dao, Sung Soo Mun, +11 authors, David A Scheinberg.
Oncoimmunology, 2019 May 31; 8(7). PMID: 31143508    Free PMC article.
Formaldehyde exposure induces regulatory T cell-mediated immunosuppression via calcineurin-NFAT signalling pathway.
Jeongsik Park, Hyo-Seon Yang, +2 authors, Kyuhong Lee.
Sci Rep, 2020 Oct 14; 10(1). PMID: 33046725    Free PMC article.
Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas.
Shengchao Xu, Lu Tang, +2 authors, Zhixiong Liu.
Front Cell Dev Biol, 2020 Nov 27; 8. PMID: 33240891    Free PMC article.
Is AAV-delivered IL-27 a potential immunotherapeutic for cancer?
Jin-Qing Liu, Jianmin Zhu, +6 authors, Xue-Feng Bai.
Am J Cancer Res, 2020 Dec 10; 10(11). PMID: 33294255    Free PMC article.
Review.
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.
The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment.
Maximilian Haist, Henner Stege, Stephan Grabbe, Matthias Bros.
Cancers (Basel), 2021 Jan 13; 13(2). PMID: 33430105    Free PMC article.
Review.
The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities.
Fatemeh Bayati, Mahsa Mohammadi, +3 authors, Ehsan Sharif-Paghaleh.
Front Immunol, 2021 Feb 02; 11. PMID: 33519807    Free PMC article.
Review.
A high number of PD-L1+ CD14+ monocytes in peripheral blood is correlated with shorter survival in patients receiving immune checkpoint inhibitors.
Kiyohiro Ando, Kazuyuki Hamada, +14 authors, Satoshi Wada.
Cancer Immunol Immunother, 2020 Aug 07; 70(2). PMID: 32757055
Involvement of Cellular Prion Protein in Invasion and Metastasis of Lung Cancer by Inducing Treg Cell Development.
Seunghwa Cha, Mi-Ji Sin, +4 authors, Mi-Yeon Kim.
Biomolecules, 2021 Mar 07; 11(2). PMID: 33671884    Free PMC article.
T Cell Subsets During Early Life and Their Implication in the Treatment of Childhood Acute Lymphoblastic Leukemia.
Shanie Saghafian-Hedengren, Eva Sverremark-Ekström, Anna Nilsson.
Front Immunol, 2021 Mar 26; 12. PMID: 33763058    Free PMC article.
Review.
Small molecule inhibitors against PD-1/PD-L1 immune checkpoints and current methodologies for their development: a review.
Chang Liu, Navindra P Seeram, Hang Ma.
Cancer Cell Int, 2021 Apr 29; 21(1). PMID: 33906641    Free PMC article.
Review.
Identification and Validation of an Immune-Associated RNA-Binding Proteins Signature to Predict Clinical Outcomes and Therapeutic Responses in Glioma Patients.
Ruotong Tian, Yimin Li, Qian Liu, Minfeng Shu.
Cancers (Basel), 2021 May 01; 13(7). PMID: 33917399    Free PMC article.
FOXP3-based immune risk model for recurrence prediction in small-cell lung cancer at stages I-III.
Minlin Jiang, Chunyan Wu, +13 authors, Caicun Zhou.
J Immunother Cancer, 2021 May 20; 9(5). PMID: 34006632    Free PMC article.
Near Infrared Photoimmunotherapy; A Review of Targets for Cancer Therapy.
Takuya Kato, Hiroaki Wakiyama, +2 authors, Hisataka Kobayashi.
Cancers (Basel), 2021 Jun 03; 13(11). PMID: 34064074    Free PMC article.
Review.
Turning 'Cold' tumors 'Hot': immunotherapies in sarcoma.
Jeff Rytlewski, Mohammed M Milhem, Varun Monga.
Ann Transl Med, 2021 Jul 20; 9(12). PMID: 34277839    Free PMC article.
Review.
The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target.
Manqiu Ding, Yongqiang Chen, Yue Lang, Li Cui.
Front Oncol, 2021 Oct 02; 11. PMID: 34595121    Free PMC article.
Review.
Hypoxia-Related lncRNA Correlates With Prognosis and Immune Microenvironment in Lower-Grade Glioma.
Shengchao Xu, Lu Tang, +2 authors, Quan Cheng.
Front Immunol, 2021 Oct 19; 12. PMID: 34659218    Free PMC article.
Elimination of acquired resistance to PD-1 blockade via the concurrent depletion of tumour cells and immunosuppressive cells.
Gang Xue, Ziyu Wang, +6 authors, Yong Lu.
Nat Biomed Eng, 2021 Nov 03; 5(11). PMID: 34725506    Free PMC article.
Spatiotemporal depletion of tumor-associated immune checkpoint PD-L1 with near-infrared photoimmunotherapy promotes antitumor immunity.
Shunichi Taki, Kohei Matsuoka, +6 authors, Kazuhide Sato.
J Immunother Cancer, 2021 Nov 03; 9(11). PMID: 34725216    Free PMC article.
Development and Verification of the Amino Metabolism-Related and Immune-Associated Prognosis Signature in Gliomas.
Yang Xu, Liguo Ye, +5 authors, Qianxue Chen.
Front Oncol, 2021 Nov 23; 11. PMID: 34804978    Free PMC article.
Mucosal tissue regulatory T cells are integral in balancing immunity and tolerance at portals of antigen entry.
Brianna R Traxinger, Laura E Richert-Spuhler, Jennifer M Lund.
Mucosal Immunol, 2021 Dec 01; 15(3). PMID: 34845322    Free PMC article.
Review.
Immunometabolism in biofilm infection: lessons from cancer.
Rasoul Mirzaei, Niloofar Sabokroo, +2 authors, Sajad Karampoor.
Mol Med, 2022 Jan 31; 28(1). PMID: 35093033    Free PMC article.
Review.