Skip to main content
Erschienen in: Endocrine 1/2021

03.10.2020 | Original Article

Myeloid-derived suppressor cells in gastroenteropancreatic neuroendocrine neoplasms

verfasst von: Man Liu, Yixuan Zhang, Luohai Chen, Yuan Lin, Qiao He, Yu Zeng, Minhu Chen, Jie Chen

Erschienen in: Endocrine | Ausgabe 1/2021

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat M1. Cives, J.R. Strosberg, Gastroenteropancreatic neuroendocrine tumours. CA Cancer J. Clin. 68(6), 471–487 (2018)CrossRef M1. Cives, J.R. Strosberg, Gastroenteropancreatic neuroendocrine tumours. CA Cancer J. Clin. 68(6), 471–487 (2018)CrossRef
2.
Zurück zum Zitat G. Rindi, D.S. Klimstra, B. Abedi-Ardekani et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod. Pathol. 31(12), 1770–1786 (2018)CrossRef G. Rindi, D.S. Klimstra, B. Abedi-Ardekani et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod. Pathol. 31(12), 1770–1786 (2018)CrossRef
3.
Zurück zum Zitat M. Riihimäki, A. Hemminki, K. Sundquist et al. The epidemiology of metastases in neuroendocrine tumours. Int. J. Cancer. 139(12), 2679–2686 (2016)CrossRef M. Riihimäki, A. Hemminki, K. Sundquist et al. The epidemiology of metastases in neuroendocrine tumours. Int. J. Cancer. 139(12), 2679–2686 (2016)CrossRef
4.
Zurück zum Zitat J. Kaiser, J. Couzin-Frankel, Cancer immunotherapy sweeps nobel for medicine. Science. 362(6410), 13 (2018)CrossRef J. Kaiser, J. Couzin-Frankel, Cancer immunotherapy sweeps nobel for medicine. Science. 362(6410), 13 (2018)CrossRef
5.
Zurück zum Zitat M. Cives, E. Pelle’, D. Quaresmini et al. The tumor microenvironment in neuroendocrine tumors: biology and therapeutic implications. Neuroendocrinology. 109(2), 83–99 (2019)CrossRef M. Cives, E. Pelle’, D. Quaresmini et al. The tumor microenvironment in neuroendocrine tumors: biology and therapeutic implications. Neuroendocrinology. 109(2), 83–99 (2019)CrossRef
6.
Zurück zum Zitat MatthiasM. Weber, Christian Fottner, Immune checkpoint inhibitors in the treatment of patients with neuroendocrine neoplasia. Oncol. Res. Treat. 41(5), 306–312 (2018)CrossRef MatthiasM. Weber, Christian Fottner, Immune checkpoint inhibitors in the treatment of patients with neuroendocrine neoplasia. Oncol. Res. Treat. 41(5), 306–312 (2018)CrossRef
7.
Zurück zum Zitat Wu-Hu Zhang, Wen-Quan Wang, He-Li Gao et al. The tumor immune microenvironment in gastroenteropancreatic neuroendocrine neoplasms. Biochim. Biophys. Acta Rev. Cancer 1872(2), 188311 (2019)CrossRef Wu-Hu Zhang, Wen-Quan Wang, He-Li Gao et al. The tumor immune microenvironment in gastroenteropancreatic neuroendocrine neoplasms. Biochim. Biophys. Acta Rev. Cancer 1872(2), 188311 (2019)CrossRef
8.
Zurück zum Zitat K. Nakamura, M.J. Smyth, Myeloid immunosuppression and immune checkpoints in the tumor microenvironment. Cell Mol. Immunol. 17(1), 1–12 (2020)CrossRef K. Nakamura, M.J. Smyth, Myeloid immunosuppression and immune checkpoints in the tumor microenvironment. Cell Mol. Immunol. 17(1), 1–12 (2020)CrossRef
9.
Zurück zum Zitat A. Silva, M. Bowden, S. Zhang et al. Characterization of the neuroendocrine tumor immune microenvironment. Pancreas. 47(9), 1123–1129 (2018)CrossRef A. Silva, M. Bowden, S. Zhang et al. Characterization of the neuroendocrine tumor immune microenvironment. Pancreas. 47(9), 1123–1129 (2018)CrossRef
10.
Zurück zum Zitat M. Cives, J. Strosberg, S.A.L. Diffalha et al. Analysis of the immune landscape of small bowel neuroendocrine tumors. Endocr. Relat. Cancer. 26(1), 119–130 (2019)CrossRef M. Cives, J. Strosberg, S.A.L. Diffalha et al. Analysis of the immune landscape of small bowel neuroendocrine tumors. Endocr. Relat. Cancer. 26(1), 119–130 (2019)CrossRef
11.
Zurück zum Zitat F. Veglia, M. Perego, D. Gabrilovich, Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19(2), 108–119 (2018)CrossRef F. Veglia, M. Perego, D. Gabrilovich, Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19(2), 108–119 (2018)CrossRef
12.
Zurück zum Zitat V. Bronte, S. Brandau, S.H. Chen et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat. Commun. 7(Jul), 12150 (2016)CrossRef V. Bronte, S. Brandau, S.H. Chen et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat. Commun. 7(Jul), 12150 (2016)CrossRef
13.
Zurück zum Zitat I.D. Nagtegaal, R.D. Odze, D. Klimstra et al. The2019 WHO classification of tumours of the digestive system. Histopathology 76(2), 182–188 (2020)CrossRef I.D. Nagtegaal, R.D. Odze, D. Klimstra et al. The2019 WHO classification of tumours of the digestive system. Histopathology 76(2), 182–188 (2020)CrossRef
14.
Zurück zum Zitat D.S. Klimstra, G. Kloppell, S. La Rosa, et al. WHO classification of tumours: digestive system tumours, 5th edn, ed. by WHO Classification of Tumours Editorial Board (International Agency for Research on Cancer, Lyon, 2019) D.S. Klimstra, G. Kloppell, S. La Rosa, et al. WHO classification of tumours: digestive system tumours, 5th edn, ed. by WHO Classification of Tumours Editorial Board (International Agency for Research on Cancer, Lyon, 2019)
15.
Zurück zum Zitat M.B. Amin, F.L. Greene, S.B. Edge et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J. Clin. 67(2), 93–99 (2017)CrossRef M.B. Amin, F.L. Greene, S.B. Edge et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J. Clin. 67(2), 93–99 (2017)CrossRef
16.
Zurück zum Zitat M.B. Amin, S. Edge, F. Greene et al. AJCC Cancer Staging Manual, 8th edn. (Springer International Publishing: American Joint Commission on Cancer, New York, 2017) M.B. Amin, S. Edge, F. Greene et al. AJCC Cancer Staging Manual, 8th edn. (Springer International Publishing: American Joint Commission on Cancer, New York, 2017)
17.
Zurück zum Zitat C.P. Corkum, D.P. Ings, C. Burgess et al. Immune cell subsets and their gene expression profiles from human PBMC isolated by Vacutainer Cell Preparation Tube (CPT™) and standard density gradient. BMC Immunol. 16, 48 (2015)CrossRef C.P. Corkum, D.P. Ings, C. Burgess et al. Immune cell subsets and their gene expression profiles from human PBMC isolated by Vacutainer Cell Preparation Tube (CPT™) and standard density gradient. BMC Immunol. 16, 48 (2015)CrossRef
18.
Zurück zum Zitat G. Chen, A.C. Huang, W. Zhang et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 560(7718), 382–386 (2018)CrossRef G. Chen, A.C. Huang, W. Zhang et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 560(7718), 382–386 (2018)CrossRef
19.
Zurück zum Zitat R.B. Holmgaard, D. Zamarin, Y. Li et al. Tumour-expressed IDO recruits and activates MDSCs in a treg-dependent manner. Cell Rep. 13(2), 412–424 (2015)CrossRef R.B. Holmgaard, D. Zamarin, Y. Li et al. Tumour-expressed IDO recruits and activates MDSCs in a treg-dependent manner. Cell Rep. 13(2), 412–424 (2015)CrossRef
20.
Zurück zum Zitat M. Liu, J. Zhou, X. Liu et al. Targeting monocyte-intrinsic enhancer reprogramming improves immunotherapy efficacy in hepatocellular carcinoma. Gut. 69(2), 365–379 (2020)CrossRef M. Liu, J. Zhou, X. Liu et al. Targeting monocyte-intrinsic enhancer reprogramming improves immunotherapy efficacy in hepatocellular carcinoma. Gut. 69(2), 365–379 (2020)CrossRef
21.
Zurück zum Zitat M. Pavel, D. O’Toole, F. Costa et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 103(2), 172–185 (2016)CrossRef M. Pavel, D. O’Toole, F. Costa et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 103(2), 172–185 (2016)CrossRef
22.
Zurück zum Zitat D.F. Quail, J.A. Joyce, Microenvironmental regulation of tumour progression and metastasis. Nat. Med. 19(11), 1423–1437 (2013)CrossRef D.F. Quail, J.A. Joyce, Microenvironmental regulation of tumour progression and metastasis. Nat. Med. 19(11), 1423–1437 (2013)CrossRef
23.
Zurück zum Zitat J.E. Talmadge, D.I. Gabrilovich, History of myeloid-derived suppressor cells. Nat. Rev. Cancer. 13(10), 739–752 (2013)CrossRef J.E. Talmadge, D.I. Gabrilovich, History of myeloid-derived suppressor cells. Nat. Rev. Cancer. 13(10), 739–752 (2013)CrossRef
24.
Zurück zum Zitat V. Kumar, S. Patel, E. Tcyganov et al. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol. 37(3), 208–220 (2016)CrossRef V. Kumar, S. Patel, E. Tcyganov et al. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol. 37(3), 208–220 (2016)CrossRef
25.
Zurück zum Zitat T. Condamine, I. Ramachandran, J. I. Youn, et al. Regulation of tumour metastasis by myeloid-derived suppressor cells. Annu. Rev. Med. 66, 97–110 (2015)CrossRef T. Condamine, I. Ramachandran, J. I. Youn, et al. Regulation of tumour metastasis by myeloid-derived suppressor cells. Annu. Rev. Med. 66, 97–110 (2015)CrossRef
26.
Zurück zum Zitat M. Ouzounova, E. Lee, R. Piranlioglu et al. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat. Commun. 8(Apr), 14979 (2017)CrossRef M. Ouzounova, E. Lee, R. Piranlioglu et al. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat. Commun. 8(Apr), 14979 (2017)CrossRef
27.
Zurück zum Zitat Y. Wang, Y. Ding, N. Guo et al. MDSCs: key criminals of tumour pre-metastatic niche formation. Front. Immunol. 10(Feb), 172 (2019)CrossRef Y. Wang, Y. Ding, N. Guo et al. MDSCs: key criminals of tumour pre-metastatic niche formation. Front. Immunol. 10(Feb), 172 (2019)CrossRef
28.
Zurück zum Zitat P.T. Nghiem, S. Bhatia, E. J. Lipson et al. PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N. Engl. J. Med. 374(26), 2542–2552 (2016)CrossRef P.T. Nghiem, S. Bhatia, E. J. Lipson et al. PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N. Engl. J. Med. 374(26), 2542–2552 (2016)CrossRef
29.
Zurück zum Zitat S.J. Antonia, J.A. López-Martin, J. Bendell et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 17(7), 883–895 (2016)CrossRef S.J. Antonia, J.A. López-Martin, J. Bendell et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 17(7), 883–895 (2016)CrossRef
30.
Zurück zum Zitat M. Guida, A. D’Alò, A. Mangia et al. Somatostatin receptors in merkel-cell carcinoma: a therapeutic opportunity using somatostatin analog alone or in association with checkpoint inhibitors immunotherapy. A case report. Front Oncol. 10, 1073 (2020)PubMed M. Guida, A. D’Alò, A. Mangia et al. Somatostatin receptors in merkel-cell carcinoma: a therapeutic opportunity using somatostatin analog alone or in association with checkpoint inhibitors immunotherapy. A case report. Front Oncol. 10, 1073 (2020)PubMed
Metadaten
Titel
Myeloid-derived suppressor cells in gastroenteropancreatic neuroendocrine neoplasms
verfasst von
Man Liu
Yixuan Zhang
Luohai Chen
Yuan Lin
Qiao He
Yu Zeng
Minhu Chen
Jie Chen
Publikationsdatum
03.10.2020
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2021
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-020-02467-2

Weitere Artikel der Ausgabe 1/2021

Endocrine 1/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.