Regulatory T Cells and Immunotherapy for Gliomas

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1 ISSN CN / Q http / /cjbmb bjmu edu cn Chinese Journal of Biochemistry and Molecular Biology ~ 139 DOI /j cnki cjbmb T * T regulatory T cell CD 4 + T CD 8 + T NK B T R73 Regulatory T Cells and Immunotherapy for Gliomas FENG Jian-Bo WU Ming-Hua * LI Gui-Yuan Cancer Research Institute of Central South University Changsha China Abstract Regulatory T cell is a cell type that negatively regulates other immune cells suppresses the activation and proliferation of CD 4 + and CD 8 + lymphocytes NK cells B lymphocytes and dendritic cells to keep the stability of immune system and to avoid the occurrence of autoimmune diseases In recent research cells was known to a play critical role in tumors as tumor cells can suppress immune response by propagating or recruiting cells This suggested that the role of may be significant in tumorigenesis and progression Therefore reducing the number or activation of cells could be an effective way to improve the immunotherapy of tumors including glioma Key words regulatory T cell immune escape glioma immunotherapy T CD 4 + CD 25 + FoxP T 1995 Sakaguchi 1 CD 4 + CD 25 + T CD 4 CD 25 CD 4 + CD 25 + T No * Tel wuminghua554@ aliyun com Received August Accepted September Supported by National Natural Science Foundation of China No * Corresponding author Tel wuminghua554@ aliyun com

2 CD4 + CD8 + NK CD4 + CD CD4 + CD 4 + thymus-derived regulatory T cell t CD CD 8 + peripherally derived regulatory T cell pcd 8 + CD 8 + CD 28- CD8 + in vitro-induced regulatory T cell i 4 T CD4 + CD8 + CD 4 + Foxp3 T Foxp3 5 MS CD 4 + CD 25 + CD 4 + CD 25 + CD 4 + CD 25 + CD4 + T 5% ~ 10% T T CD 8 + IL-2 /IFNγ 6 CD 4 + CD 25 + CD4 2 α CD25 CD8 + CD8 + T 4 cytotoxic T lymphocyteassociated antigen-4 CTLA-4 T 5% ~ 10% glucocorticoid-induced tumor necrosis factor receptor GITR CD 4 + CD NK 2 Foxp3 T CD56 bright CD16 - NK CD56 dim CD16 + NK CD56 dim CD16 + NK 90% Foxp3 T 10% CD56 bright CD16 - CD127 Foxp3 + CD127 NK CD 4 + CD 25 + CD127 Tian CD 4 + CD 25 + CD NK CD 4 + CD 25 + Verneris 13 NK Foxp3 7 CD 4 + CD 25 + NK T 2 IL-2 NK T T cell antigen receptor TCR NK B CD8 + CD 8 + CD 8 + CD 8 + CD 8 + CD 8 + CD 25 + CD 8 + Foxp3 + Kouchaki 10 CD8 + CD8 + IL-6 IL-10 CD NK NK T CD3 - CD56 + CD3 - CD56 + allo-hct CD 4 + CD 8 + T NK 1 2 CD4 + CD8 + T B APC antigen presenting cell CD 4 + CD 25 + CD8 + T

3 2 T major CTLA-4 histocompatibility complex MHC IL-2 T CTLA-4 CTLA TGF-β IL-10 1 MHC TGF-β B7H1 TGF-β B7-H1 i 1 programmed death-1 TGF-β PD-1 T 17 2 NK Ig IFN-γ IL-2 B IL IL-10 cyclooxygenase COX A E2 prostaglandin E2 PGE2 1 3 PGE2 inductible nitric oxide synthase inos vascular endothelial growth factor VEGF T 18 DC IL-2 IFN-α PGE2 COX-2-1 inhibitor of differentiation-1 ID T T 3 CD 4 + CD 25 + Foxp3 T 2 Ⅱ- 2 1 FasL TGF-β PGE Ⅲ-Ⅳ 20 Wainwright 21

4 natural regulatory T cell n induced regulatory T cell i References n n n i n i n i CD 4 + T i n n i Neuropilin-1 Helios n i n i foxp3 + CCL2 CC chemokine ligand % CCL2 CCR4 CC chemokine receptor 4 34% 22 CCL2 CCR Sakaguchi S Sakaguchi N Asano M et al Immunologic selftolerance maintained by activated T cells expressing IL-2 receptor α-chains CD25 multiple sclerosis J 255 with interferon-α J autoimmune disease J Hematol Educ Program 14 J Breakdown of a single mechanism of selftolerance causes various autoimmune diseases J J Immunol Curiel T J Regulatory T cells and treatment of cancer J Curr Opin Immunol Wainwright D A Dey M Chang A et al Targeting s in malignant brain cancer overcoming IDO J Front Immunol Abbas A K Benoist C Bluestone J A et al Regulatory T cells recommendations to simplify the nomenclature J Nat Immunol Curotto de Lafaille M A Lafaille J J Natural and adaptive regulatory T cells more of the same or a division of labor J Immunity Duan M C Zhong X N Liu G N et al The /Th17 paradigm in lung cancer J J Immunol Res Liu W Putnam A L Zhou X Y et al CD127 expression inversely correlates with FoxP3 and suppressive function of human CD 4 + cells J J Exp Med Zhao E Wang L Dai J et al Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer J Oncoimmunology Ganesan A P Johansson M Ruffell B et al Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma J J Immunol Kouchaki E Salehi M Reza Sharif M et al Numerical status of CD4 + CD25 + FoxP3 + and CD8 + CD28 - regulatory T cells in Iran J Basic Med Sci Riley C H Hansen M Brimnes M K et al Expansion of circulating CD56 bright natural killer cells in patients with JAK2- positive chronic myeloproliferative neoplasms during treatment Eur J Haematol 2014 doi / ejh Epub ahead of print 12 Tian Z Gershwin M E Zhang C Regulatory NK cells in J Autoimmun Verneris M R Natural killer cells and regulatory T cells how to manipulate a graft for optimal GVL J Hematology Am Soc T Fan M Huo J G Advancement in the research on regulatory T cell in tumor immune escape and China traditional medicine treatment J J

5 2 T 139 Zhejiang Univ Tradit Chin Med Cribbs A P Kennedy A Penn H et al Regulatory T cell function in rheumatoid arthritis is compromised by CTLA-4 promoter methylation resulting in a failure to activate the IDO pathway J Arthritis Rheumatol Kim S Buchlis G Fridlender Z G et al Systemic blockade of transforming growth factor-beta signaling augments the efficacy of immunogene therapy J Cancer Res Yao Y Tao R Wang X et al B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells J Neuro Oncol El-Sayed M Taha M M Immunohistochemical expression of cycloxygenase-2 in astrocytoma correlation with angiogenesis tumor progression and survival J Turk Neurosurg Xu K Wang L Shu H K COX-2 overexpression increases malignant potential of human glioma cells through Id1 J Oncotarget Heimberger A B Abou-Ghazal M Reina-Ortiz C et Incidence and prognostic impact of FoxP3 + regulatory T cells in human gliomas J Clin Cancer Res Wainwright D A Sengupta S Han Y et al Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors J Neuro Oncol Jordan J T Sun W Hussain S F et al Preferential migration of regulatory T cells mediated by glioma-secreted chemokines can be blocked with chemotherapy J Cancer Immunol Immunother Jacobs J F Idema A J Bol K F et al Prognostic significance and mechanism of infiltration in human brain tumors J J Neuroimmunol al