Myeloid-derived suppressor cells in gastroenteropancreatic neuroendocrine neoplasms
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ORIGINAL ARTICLE
Myeloid-derived suppressor cells in gastroenteropancreatic neuroendocrine neoplasms Man Liu1 Yixuan Zhang1 Luohai Chen1 Yuan Lin2 Qiao He3 Yu Zeng3 Minhu Chen1 Jie Chen1 ●
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Received: 24 March 2020 / Accepted: 19 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 GEPNEN 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. Keywords Myeloid-derived suppressor cells Metastasis Gastroenteropancreatic neuroendocrine neoplasms Immune microenvironment ●
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Introduction
These authors contributed equally: Man Liu, Yixuan Zhang, Luohai Chen Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02467-2) contains supplementary material, which is available to authorized users. * Minhu Chen [email protected] * Jie Chen [email protected] 1
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are a heterogeneous group of tumors arising from the gastro-intestinal tract and pancreas. The clinical behaviors of GEP-NENs are highly variable and unpredictable, with median survival ranging from ~6 months in high grade aggressive cases to up to 20 years in more indolent cases [1]. Tumor differentiation and proliferation index determine the tumor grade and both have been defined as prognostic factors for GEP-NENs [2]. However, the cur
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