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Myeloid-derived suppressor cells in gastroenteropancreatic neuroendocrine neoplasms

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Abstract

Background

Expanded myeloid-derived suppressor cells (MDSCs) correlate with disseminated metastases and poor prognosis in various human cancers. However, the role of MDSCs in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is still unknown. We investigated the distribution of MDSCs and their clinical significance in patients with GEP-NENs.

Methods

Peripheral blood mononuclear cells (PBMCs) and paraffin-embedded tumor tissues were acquired from patients with GEP-NENs. Multicolor flow cytometry was performed to determine the frequency of MDSCs in peripheral blood, and immunohistochemistry was performed to determine the distribution of MDSCs in primary NEN tissues.

Results

Compared to healthy donors, patients with GEP-NENs had significantly higher levels of circulating monocytic (M)-MDSCs. Frequency of M-MDSCs in both peripheral blood and primary NEN tissues was significantly higher in GEP-NEN patients with metastases compared to patients without metastases. Tumor-infiltrating M-MDSCs can serve as a valuable prognostic marker of metastasis in patients with GEP-NENs, as indicated by the area under the curve (AUC) = 0.71; 95% confidence interval (CI) = 0.56–0.87, p < 0.01.

Conclusions

High M-MDSC levels were associated with significantly increased metastases in patients with GEP-NENs. M-MDSCs appear to be a promising prognostic immunologic biomarker and therapeutic target in GEP-NEN management.

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Funding

The study was funded by the China Post-doctoral Science Foundation (2018M640872) and Natural Science Foundation of Guangdong Province (2019A1515011373 and 2019A1515012027).

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Author notes

  1. These authors contributed equally: Man Liu, Yixuan Zhang, Luohai Chen

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Man Liu, Yixuan Zhang, Luohai Chen, Minhu Chen & Jie Chen

  2. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Yuan Lin

  3. Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Qiao He & Yu Zeng

Authors
  1. Man Liu
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  2. Yixuan Zhang
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  3. Luohai Chen
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  4. Yuan Lin
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  5. Qiao He
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  6. Yu Zeng
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  7. Minhu Chen
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  8. Jie Chen
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Contributions

M.L. and J.C. designed the study. M.L. performed the statistical analysis and prepared the initial draft. M.L. performed the experiment, Y.X.Z. and L.H.C. collected the samples and assisted in data collection. Y.L. provided technical support in histology. Q.H. and Y.Z. provided technical support in imaging analysis. M.H.C. conceived the study, participated in its design and contributed to the revision of the paper. All authors provided input and approved the final version.

Corresponding authors

Correspondence to Minhu Chen or Jie Chen.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by Institutional Ethics Committee for clinical research and animal trials of the First Affiliated Hospital of Sun Yat-sen University.

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All subjects provided informed consent to participate in the study.

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Liu, M., Zhang, Y., Chen, L. et al. Myeloid-derived suppressor cells in gastroenteropancreatic neuroendocrine neoplasms. Endocrine 71, 242–252 (2021). https://doi.org/10.1007/s12020-020-02467-2

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  • DOI: https://doi.org/10.1007/s12020-020-02467-2

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