Man Liu1, Yixuan Zhang1, Luohai Chen1, Yuan Lin2, Qiao He3, Yu Zeng3, Minhu Chen4, Jie Chen5. 1. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 2. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 3. Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 4. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. chenminhu@mail.sysu.edu.cn. 5. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. chen0jie@hotmail.com.
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.
BACKGROUND: Expanded myeloid-derived suppressor cells (MDSCs) correlate with disseminated metastases and poor prognosis in various humancancers. 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.