Specific Recruitment of γδ Regulatory T Cells in Human Breast Cancer

Ye, Jian; Ma, Chunling; Wang, Fang; Hsueh, Eddy C.; Tóth, Károly; Huang, Yi; Mo, Wei; Liu, Shuai; Han, Bing; Varvares, Mark A.; Hoft, Daniel F.; Peng, Guangyong

doi:10.1158/0008-5472.can-13-0348

Cited by 86 publications

(65 citation statements)

References 51 publications

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“…Previous studies have shown that gd1 T cells are the major immunosuppressive T cells in human breast cancer. 37,38 In this study, we unexpectedly discover that CD39 C gdTregs are the major regulatory T cells within the human CRC. CD39 C gdTregs not only are more in numbers compared with CD4 C Tregs but also exhibit more potent immunosuppressive activity than CD4 C Tregs.…”

Section: Discussionmentioning

confidence: 78%

Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer

Cheng

et al. 2017

OncoImmunology

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Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39 C gdTreg in human colorectal cancer (CRC). CD39 C gdTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4 C or CD8 C Tregs via the adenosine-mediated pathway but independent of TGF-b or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network. We further demonstrate that tumor-derived TGF-b1 induces CD39 C gdT cells from paired normal colon tissues to produce more adenosine and become potent immunosuppressive T cells. Moreover, CD39 C gdTreg infiltration is positively correlated with TNM stage and other unfavorable clinicopathological features, implicating that CD39 C gdTregs are one of the key players in establishment of immunosuppressive TME in human CRC that may be critical for tumor immunotherapy.

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Section: Discussionmentioning

confidence: 78%

Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer

Cheng

et al. 2017

OncoImmunology

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“…Once activated, Vd1 + T cells can drive DC maturation [215] but also kill DCs [216]. In addition, Vd1 + T cells can display properties of regulatory T cells and suppress immune responses through contact or cytokine dependent interactions [217][218][219][220], including the suppression of DC maturation in breast cancer [221,222]. Thus, it appears that the Vd1 + , Vd2 + and Vd3 + subsets of cd T cells as well as iNKT cells all play roles in the induction, polarization and/or regulation of adaptive immune responses in humans.…”

Section: Innate Regulation Of Adaptive Immune Responses: Vd2 + Versusmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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“…Such gd Tregs damp antitumor immunity 33 and contribute to the immunosuppressive microenvironment that is characteristic of most tumor cells. 34 Deficient gd T cell functions have already been observed in various malignancies, including hematological, 20 liver, 35 breast 35 and gastric cancers. 36 Re-establishment of gd T cell antitumor activity is therefore valuable.…”

Section: Gd T Cells and Cancer Immunitymentioning

confidence: 99%

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Anguille

et al. 2015

OncoImmunology

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These authors equally contributed to the work.Keywords: gd T cell, cancer, DC-mediated gd T cell activation, dendritic cell, immunotherapy Abbreviations: gd, gamma delta; BCG, Bacillus Calmette-Guerin; BrHPP, bromohydrin pyrophosphate; CTL, cytotoxic T lymphocyte; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; HIV, human immunodeficiency virus; HMBPP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; iDC, immature DC; IFN, interferon; IL, interleukin; IPP, isopentyl pyrophosphate; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; mo-DC, monocyte-derived dendritic cell; pDC, plasmacytoid dendritic cell; PD, programmed cell death protein; TCR, T-cell receptor; Th, T-helper cell; TLR, toll-like receptor; TNF, tumor necrosis factor; Treg, regulatory T cellGamma delta (gd) T cells are the all-rounders of our immune-system with their major histocompatibility complexunrestricted cytotoxicity, capacity to secrete immunostimulatory cytokines and ability to promote the generation of tumor antigen-specific CD8 C and CD4 C T cell responses. Dendritic cell (DC)-based vaccine therapy has the prospective to harness these unique features of the gd T cells in the fight against cancer. In this review, we will discuss our current knowledge on DC-mediated gd T cell activation and related opportunities for tumor immunologists.

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Specific Recruitment of γδ Regulatory T Cells in Human Breast Cancer

Cited by 86 publications

References 51 publications

Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer

Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

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Specific Recruitment of γδ Regulatory T Cells in Human Breast Cancer

Cited by 86 publications

References 51 publications

Tumor-infiltrating CD39+γδTregs are novel immunosuppressive T cells in human colorectal cancer

Tumor-infiltrating CD39+γδTregs are novel immunosuppressive T cells in human colorectal cancer

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

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Product

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Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer

Tumor-infiltrating CD39⁺γδTregs are novel immunosuppressive T cells in human colorectal cancer