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Immune regulation by CD8+ Treg cells: novel possibilities for anticancer immunotherapy

Cellular & Molecular Immunology volume 15, pages 805–807 (2018)Cite this article

Cellular and Molecular Immunology advance online publication, 5 March 2018; https://doi.org/10.1038/cmi.2018.170

We recently identified the expression of Treg markers in CD8+ T cells isolated from peripheral blood and fresh tumor tissues of OC patients. We detected a higher percentage of CD8+ Treg cells in OC patients compared with benign ovarian tumor patients and healthy controls.6 The immune-suppressive T-cell markers CD25, cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Foxp3 were upregulated, whereas expression of the immune activation marker CD28 was downregulated in these cells. We also showed that levels of Foxp3 in CD8+ T cells were positively associated with tumor stage in OC patients, suggesting that CD8+Foxp3+ Treg cells contribute to the progression of OC. This highlights the role of CD8+Foxp3+ Treg cells as predictors of clinical outcome in OC patients. Then we determined whether the tumor microenvironment had the ability to convert CD8+ effector T cells into suppressor cells. We observed phenotypic similarities between CD8+ Tcells in transwell co-culture system and CD8+ T cells obtained from OC tumor tissues, including upregulated Foxp3 and CTLA-4 and downregulated CD28 expression levels.6 The in vitro-induced CD8+ Treg cells also secreted higher concentrations of transforming growth factor β1 (TGF-β1), interferon (IFN)-γ, tumor necrosis factor (TNF)-α,and interleukin (IL)−2. The Foxp3+CTLA-4+ and TGF-β1+ phenotype indicated that the induced CD8+ Treg cells were functionally activated, which was confirmed by their ability to suppress CD4+ T-cell proliferation partially by TGF-β1and IFN-γ. These data imply that CD8+ Treg cells accumulated in OC tissue in vivo and inducible in vitro may dampen antitumor immunity and contribute to tumor immune evasion.

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Acknowledgements

We are grateful to the technical support from National Key Clinical Department of Laboratory Medicine of Jiangsu Province Hospital. This study was supported by Natural Science Foundation of China (No.81772779), Jiangsu Province’sKey Provincial Talents Program (No. ZDRCA2016003) and Key Laboratory for Medicine of Jiangsu Province of China (No. ZDXKB2016005), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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  1. S. Zhang and M. Wu contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, 210008, China

    Shuping Zhang & Meng Wu

  2. Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Fang Wang

  3. National Key Clinical Department of Laboratory Medicine, Nanjing, 210029, China

    Fang Wang

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  1. Shuping Zhang
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Correspondence to Fang Wang.

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Zhang, S., Wu, M. & Wang, F. Immune regulation by CD8+ Treg cells: novel possibilities for anticancer immunotherapy. Cell Mol Immunol 15, 805–807 (2018). https://doi.org/10.1038/cmi.2018.170

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