. 2020 Jan; 11:10731-10747.
doi: 10.2147/CMAR.S228887.

T-Regulatory Cells In Tumor Progression And Therapy

Amit Verma 1 Rohit Mathur 2 Abdullah Farooque 3 Vandana Kaul 4 Seema Gupta 5 Bilikere S Dwarakanath 6 
  • PMID: 31920383
  •     174 References
  •     16 citations


Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic efficacy. Our earlier studies have shown the efficacy of the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG) by reducing the induced Tregs pool and enhance immune stimulation as well as local tumor control. These findings have suggested its potential for enhancing the efficacy of immunotherapy, besides radiotherapy and chemotherapy. This review provides a brief account of the current status of Tregs as a component of the immune-biology of tumors and various preclinical and clinical strategies pursued to obviate the limitations imposed by them in achieving therapeutic efficacy.

Keywords: 2-deoxy-D-glucose; T-regulatory cells; cyclophosphamide; dendritic cells; immune enhancement; metabolic inhibitor; targeted cancer therapy.

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CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis.
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Increased regulatory versus effector T cell development is associated with thymus atrophy in mouse models of multiple myeloma.
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PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer.
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CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative.
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Alterations in radiation induced cell cycle perturbations by 2-deoxy-D-glucose in human tumor cell lines.
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T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease.
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PD-L1 regulates the development, maintenance, and function of induced regulatory T cells.
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Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma.
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Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials.
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Advanced stage melanoma therapies: Detailing the present and exploring the future.
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Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells.
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T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases.
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Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients.
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Regulatory T cells: Folate receptor 4: a new handle on regulation and memory?
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Phase I/II trial of tremelimumab in patients with metastatic melanoma.
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Radiation Dose Escalation is Crucial in Anti-CTLA-4 Antibody Therapy to Enhance Local and Distant Antitumor Effect in Murine Osteosarcoma.
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SARS-CoV-2 cell receptor gene ACE2 -mediated immunomodulation in breast cancer subtypes.
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Biochem Biophys Rep, 2020 Nov 13; 24. PMID: 33178900    Free PMC article.
Obesity and Cancer Metastasis: Molecular and Translational Perspectives.
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Cancers (Basel), 2020 Dec 20; 12(12). PMID: 33339340    Free PMC article.
An overview of the tumor microenvironment, from cells to complex networks (Review).
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Simultaneous targeting of primary tumor, draining lymph node, and distant metastases through high endothelial venule-targeted delivery.
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Nano Today, 2021 Jan 05; 36. PMID: 33391389    Free PMC article.
Cell by cell immuno- and cancer marker profiling of non-small cell lung cancer tissue: Checkpoint marker expression on CD103+, CD4+ T-cells predicts circulating tumor cells.
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Transl Oncol, 2020 Nov 21; 14(1). PMID: 33217647    Free PMC article.
Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment.
Varun Sasidharan Nair, Reem Saleh, +2 authors, Eyad Elkord.
Cancer Immunol Immunother, 2021 Feb 04; 70(8). PMID: 33532902    Free PMC article.
Recent Advancements on Immunomodulatory Mechanisms of Resveratrol in Tumor Microenvironment.
Gagan Chhabra, Chandra K Singh, +2 authors, Nihal Ahmad.
Molecules, 2021 Apr 04; 26(5). PMID: 33802331    Free PMC article.
Radiotherapy planning parameters correlate with changes in the peripheral immune status of patients undergoing curative radiotherapy for localized prostate cancer.
Elgin Hoffmann, Frank Paulsen, +5 authors, Franziska Eckert.
Cancer Immunol Immunother, 2021 Jul 17; 71(3). PMID: 34269847    Free PMC article.
The Right Partner in Crime: Unlocking the Potential of the Anti-EGFR Antibody Cetuximab via Combination With Natural Killer Cell Chartering Immunotherapeutic Strategies.
Hasan Baysal, Ines De Pauw, +5 authors, An Wouters.
Front Immunol, 2021 Sep 25; 12. PMID: 34557197    Free PMC article.
Regulatory T-Cells and Multiple Myeloma: Implications in Tumor Immune Biology and Treatment.
Christina Hadjiaggelidou, Eirini Katodritou.
J Clin Med, 2021 Oct 14; 10(19). PMID: 34640606    Free PMC article.
Cyclophosphamide enhances the antitumor potency of GITR engagement by increasing oligoclonal cytotoxic T cell fitness.
Daniel Hirschhorn, Allison Betof Warner, +11 authors, Jedd D Wolchok.
JCI Insight, 2021 Oct 23; 6(20). PMID: 34676831    Free PMC article.
A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model.
Yun Hu, Sébastien Paris, +12 authors, James W Welsh.
J Nanobiotechnology, 2021 Dec 14; 19(1). PMID: 34895262    Free PMC article.
Can Immune Suppression and Epigenome Regulation in Placenta Offer Novel Insights into Cancer Immune Evasion and Immunotherapy Resistance?
Sultana Mehbuba Hossain, Chiemi F Lynch-Sutherland, +2 authors, Michael R Eccles.
Epigenomes, 2021 Dec 31; 5(3). PMID: 34968365    Free PMC article.
Naringenin and cryptotanshinone shift the immune response towards Th1 and modulate T regulatory cells via JAK2/STAT3 pathway in breast cancer.
Shokoofe Noori, Mitra Nourbakhsh, +3 authors, Zohreh Abdolvahabi.
BMC Complement Med Ther, 2022 May 24; 22(1). PMID: 35606804