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Retinoblastoma cell-derived Twist protein promotes regulatory T cell development

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Abstract

Background

The development of tumor tissue-infiltrating regulatory T cell (Treg) is incompletely understood. This study investigates the role of retinoblastoma cell (Rbc)-derived Twist‑related protein 1 (Twist) in the Treg development.

Methods

The surgically removed Rb tissues were collected. Rbcs were cultured with CD4+ T cells to assess the role of Rbc-derived Twist in the Treg generation.

Results

We found that more than 90% Rbcs expressed Twist. Foxp3+ Tregs were detected in the Rb tissues that were positively correlated with the Twist expression in Rbcs, negatively associated with Rb patient survival and sight survival. Treating Rbcs with hypoxia promoted the Twist expression that could be detected in the cytoplasm, nuclei and on the cell surface. Twist activated CD4+ T cells by binding the TLR4/myeloid differentiation factor 2 complex and promoted the transforming growth factor-β-inducible early gene 1 product and Foxp3 expression. These Rbc-induced Foxp3+ Tregs showed immune-suppressive function on CD8+ T cell proliferation.

Conclusions

Rbcs express Twist, that induces IL-4+ Foxp3+ Tregs; the latter can inhibit CD8+ cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb.

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Acknowledgements

This study was supported by grants of the National Nature and Science Foundation of China (81870706, 31570932, U1801286, 31000713, 31700805), Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009), Cross Innovation Research Initiative Funds of Shenzhen University and Shenzhen science, technology and innovation committee (201002052, KQTD20170331145453160 and KQJSCX20180328095619081).

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Author notes

  1. Ruishi Zhang and Yan-Nan Song equally contributed to this work.

Authors and Affiliations

  1. Department of Ophthalmology, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China

    Ruishi Zhang & Xiaoyan Duo

  2. Shenzhen Luohu Medical Group, Shenzhen, China

    Zhihong Guo

  3. Department of Otolaryngology, Head and Neck Surgery, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China

    Yongtian Lu, Beiping Miao & Guohui Nie

  4. Department of Pathology, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China

    Yanhua Sun & Zhixiong Zhang

  5. Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Room A7-509, Lihu Campus, 1066 Xueyuan Blvd, Shenzhen, 518055, China

    Yan-Nan Song & Ping-Chang Yang

  6. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China

    Ping-Chang Yang

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  1. Ruishi Zhang
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Contributions

RZ, YNS, XD, ZG, YS, ZZ and YL performed experiments, analyzed data and reviewed the manuscript. GN, PCY and BPM organized the study and supervised experiments. PCY designed the project and prepared manuscript.

Corresponding authors

Correspondence to Beiping Miao, Ping-Chang Yang or Guohui Nie.

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Zhang, R., Song, YN., Duo, X. et al. Retinoblastoma cell-derived Twist protein promotes regulatory T cell development. Cancer Immunol Immunother 70, 1037–1048 (2021). https://doi.org/10.1007/s00262-020-02744-z

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  • DOI: https://doi.org/10.1007/s00262-020-02744-z

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