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

Hu, Guoming; Wu, Pin; Cheng, Pu; Zhang, Zhigang; Wang, Zhen; Yu, Xijie; Shao, Xuan; Wu, Dang; Ye, Jun; Zhang, Tao; Wang, Xiaochen; Qiu, Fuming; Yan, Jun; Huang, Jian

doi:10.1080/2162402x.2016.1277305

Cited by 84 publications

(106 citation statements)

References 49 publications

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“…Human NK cells can be modulated through activation of P2Y11R (20) and, therefore, CD39 can inhibit NK cells-mediated damage. There is indeed the case that CD39 deletion has been followed by the deficiency of IFN-γ by NK cells.…”

Section: Cd39 Expressed On Different Populations Of Immune Cellsmentioning

confidence: 99%

What Else Can CD39 Tell Us?

et al. 2017

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As the rate-limiting enzyme in ATP/ADP–AMP–adenosine pathway, CD39 would be a novel checkpoint inhibitor target in preventing adenosine-triggered immune-suppressive effect. In addition, CD39hi Tregs, but not CD25hi Tregs, exhibit sustained Foxp3 levels and functional abilities, indicating it could represent a new specific marker of Tregs. Similarly, inhibition of CD39 enzymatic function at the surface of tumor cells alleviates their immunosuppressive activity. Far from conclusive, present research revealed that CD39 also dephosphorylated and thus inactivated self- and pathogen-associated phosphoantigens of Vγ9Vδ2 T cells, which may be the most promising subpopulation for cellular vaccine. CD39 is also tightly related to Th17 cells and can be regarded as a Th17 cells marker. In this review, we focus on present research of CD39 ectoenzyme and provide insights into its clinical application.

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Section: Cd39 Expressed On Different Populations Of Immune Cellsmentioning

confidence: 99%

What Else Can CD39 Tell Us?

et al. 2017

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“…Atsushi et al. proposed that CD39 was a candidate surface marker for regulatory γδ T cells in IL‐10 knockout mice, which has been confirmed by further in‐depth studies . Peters et al.…”

Section: Regulatory γδ Cellsmentioning

confidence: 91%

The expanding family of noncanonical regulatory cell subsets

Zhao

Feng

Peng

et al. 2019

Journal of Leukocyte Biology

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The overwhelming body of research on regulatory lymphocytes has focused on CD4+ CD25+ Foxp3+ T cells (regulatory T cells); however, the last 5 years have witnessed inspiring progress in our understanding of regulatory B cells, regulatory CD8+ T cells, regulatory γδ cells, and, more recently, regulatory innate lymphoid cells(ILCregs). This review focuses on these so‐called noncanonical regulatory cell subsets. We primarily survey existing information on the phenotype, function, sustaining factors, and clinical value of the 4 best‐characterized non‐CD4 +Foxp3+ T regulatory cells. We then take a brief journey into the advances and challenges associated with next‐generation sequencing technologies and the application of sequencing to the study of noncanonical regulatory cell subsets.

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“…37 In vivo tumor-infiltrating reg cells could be induced by IP-10 secreted by breast cancer cells 38 indicating that these cells may play an important role to induce the immunosuppressive microenvironment in human CRC. 40 Finally, as demonstrated by several studies on different cancer, T cells showed a dual role in tumor immunity and it seems clearly associated with their complex surrounding microenvironment, which influences T cell polarization.…”

Section: T Cellsmentioning

confidence: 91%

“…have identified a novel CD39 + γδreg cell population in CRC that exerts an immunosuppressive activity via the adenosine‐mediated pathway; these cells also secrete cytokines including IL‐17A and GM‐CSF that are able to chemoattract MDSCs, thus establishing an immunosuppressive network. Concerning their protumoral functions, the authors showed that CD39 + γδreg infiltration was positively correlated with the tumour node metastasis (TNM) stage and other unfavorable clinicopathological features, indicating that these cells may play an important role to induce the immunosuppressive microenvironment in human CRC …”

Section: γδ and Cancermentioning

confidence: 99%

γδ cells and tumor microenvironment: A helpful or a dangerous liason?

Presti

Mitri

Pizzolato

et al. 2017

Journal of Leukocyte Biology

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γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumors. γδ T cells are endowed with antitumor activities, and hence several γδ T cell-based small-scale clinical trials have been conducted either by in vivo activation by intravenous administration of aminobiphosphonates or by adoptive transfer of in vitro expanded γδ T cells. Although both these strategies have yielded promising results, there are a number of limitations associated with each of them which, if overcome may help to further improve efficacy. One of the most important limits is the possible polarization of tumor-infiltrating γδ T cells toward different γδ T cells population with functional activities that help the progression and spread of the tumor. Here, we review the modalities and the possible mechanisms involved in the polarization of tumor-infiltrating γδ T cells upon interaction with several components of the tumor microenvironment and discuss their implications for the manipulation of γδ T cells in cancer immunotherapy.

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

Cited by 84 publications

References 49 publications

What Else Can CD39 Tell Us?

What Else Can CD39 Tell Us?

The expanding family of noncanonical regulatory cell subsets

γδ cells and tumor microenvironment: A helpful or a dangerous liason?

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