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Patients with radiation enteritis present regulatory T cell impairment associated with CTLA-4

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Abstract

Radiation enteritis is one of the most common side effects of ionizing radiation in patients with pelvic cancers. Increasing amounts of evidence indicate that pro-inflammatory responses significantly contribute to the development of radiation enteritis. In this study, we investigated the association between T regulatory (Treg) cells and the risk of developing radiation enteritis in cervical cancer patients. The following observations were made. First, the frequencies of CD25hiFoxp3+ Treg cells were significantly lower in patients with radiation enteritis than in both healthy subjects and cervical cancer patients without radiation enteritis. Also, patients with the more severe grade 3 enteritis presented significantly lower Treg levels than patients with the more common grade 1 enteritis. Second, the expression of several molecules associated with Treg function, including CTLA-4, IL-10, TGF-β, and perforin, was significantly lower in patients with radiation enteritis than in healthy subjects. In patients without radiation enteritis, however, only CTLA-4, but not other Treg-associated suppressive molecules, was reduced in Treg cells. Third, Treg cells can markedly suppress CD8 T cell proliferation, but in patients with radiation enteritis, this function of Treg cells was significantly impaired, in a manner that was associated with lower CTLA-4 expression. Overall, these data suggest that the frequency and function of Treg cells is negatively associated with the risk of developing enteritis following radiation. In clinical practice, the characteristics of Treg cells may be considered to evaluate the risk of developing enteritis if the cancer patient is receiving ionizing radiation.

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Funding

This work was supported by Huzhou Science and Technology Plan Project (2018GY09).

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Author notes

  1. Xufeng Gong and Genhua Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Radiotherapy, Huzhou Zhebei Mingzhou Hospital, Huzhou, Zhejiang, China

    Xufeng Gong, Genhua Yu, Yan Hou, Ning Wang, Wei Zhao, Jingjing Ouyang, Zhengzhou Gu, Haili Hu & Lei Fei

  2. Department of Oncology, Tianyou Hospital Affiliated to Tongji University, Shanghai, China

    Zongchang Song

  3. Department of Neurology, Tianyou Hospital Affiliated to Tongji University, Shanghai, China

    Shuqi Huang

  4. Department of Pediatrics, Huzhou Hospital of Traditional Chinese medicine, Huzhou, Zhejiang, China

    Aixia Fu

  5. Medical Department, Huzhou Zhebei Mingzhou Hospital, Huzhou, Zhejiang, China

    Jingping Xia

  6. Outpatient Department, Huzhou Maternity and Child Health Care Hospital, No.2 Dongjie Road, Huzhou, Zhejiang, China

    Yuehua Ding

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  1. Xufeng Gong
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  2. Genhua Yu
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  3. Zongchang Song
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  5. Yan Hou
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  7. Wei Zhao
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  14. Yuehua Ding
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Correspondence to Yuehua Ding.

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Ethical approval was received from the Ethics Committee of Zhebei Mingzhou Hospital.

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All study participants gave written informed consent for the collection of clinical data and peripheral blood mononuclear cell (PBMC) samples.

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Gong, X., Yu, G., Song, Z. et al. Patients with radiation enteritis present regulatory T cell impairment associated with CTLA-4. Immunol Res 68, 179–188 (2020). https://doi.org/10.1007/s12026-020-09142-8

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  • DOI: https://doi.org/10.1007/s12026-020-09142-8

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