TY - JOUR
T1 - Lanreotide Induces Cytokine Modulation in Intestinal Neuroendocrine Tumors and Overcomes Resistance to Everolimus
AU - Sciammarella, Concetta
AU - Luce, Amalia
AU - Riccardi, Ferdinando
AU - Mocerino, Carmela
AU - Modica, Roberta
AU - Berretta, Massimiliano
AU - Misso, Gabriella
AU - Cossu, Alessia Maria
AU - Colao, Annamaria
AU - Vitale, Giovanni
AU - Necas, Alois
AU - Fedacko, Jan
AU - Galdiero, Marilena
AU - Correale, Pierpaolo
AU - Faggiano, Antongiulio
AU - Caraglia, Michele
AU - Capasso, Anna
AU - Grimaldi, Anna
N1 - Funding Information:
Funding. This work has been supported by IPSEN, by the NSP project nos. LO1508 and LO1309, MZ-VES project nos. 16-28637A, 16-2960A, and 17-32285A, by funds institutional research (TA29) of UVPS Brno and by AIRC (IG 2017, code 20711). The funder (IPSEN) was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Publisher Copyright:
© Copyright © 2020 Sciammarella, Luce, Riccardi, Mocerino, Modica, Berretta, Misso, Cossu, Colao, Vitale, Necas, Fedacko, Galdiero, Correale, Faggiano, Caraglia, Capasso and Grimaldi.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/7
Y1 - 2020/7/7
N2 - Somatostatin analogs mantain their major role in the treatment of patients with advanced neuroendocrine tumors (NETs) and have multiple modulatory effects on the immune system. Here, we evaluated the effects of lanreotide treatment on expression of Th1, Th2 cytokine patterns in serum of patients with NETs and in bronchial and pancreatic NET cell lines. Our results showed that lanreotide treatment promoted a Th1 cytotoxic immune-phenotype in patients with NETs originated by intestinal sites. Similar results were obtained also in vitro where lanreotide induced expression of Th1 cytokines only in pancreatic and not in bronchial-derived NET cell lines. It seems, therefore, that cytokinomics can represent a useful tool for the identification of tumor biomarkers for the early diagnosis and evaluation of the response to therapy in NET patients. To avoid the drug-resistance induced by everolimus (mTOR inhibitor), we made the pancreatic NET cell line resistant to this drug. After treatment with lanreotide we found that the drug reduced its viability compared to that of sensitive cells. These data may have direct implications in design of future translation combination trial on NET patients.
AB - Somatostatin analogs mantain their major role in the treatment of patients with advanced neuroendocrine tumors (NETs) and have multiple modulatory effects on the immune system. Here, we evaluated the effects of lanreotide treatment on expression of Th1, Th2 cytokine patterns in serum of patients with NETs and in bronchial and pancreatic NET cell lines. Our results showed that lanreotide treatment promoted a Th1 cytotoxic immune-phenotype in patients with NETs originated by intestinal sites. Similar results were obtained also in vitro where lanreotide induced expression of Th1 cytokines only in pancreatic and not in bronchial-derived NET cell lines. It seems, therefore, that cytokinomics can represent a useful tool for the identification of tumor biomarkers for the early diagnosis and evaluation of the response to therapy in NET patients. To avoid the drug-resistance induced by everolimus (mTOR inhibitor), we made the pancreatic NET cell line resistant to this drug. After treatment with lanreotide we found that the drug reduced its viability compared to that of sensitive cells. These data may have direct implications in design of future translation combination trial on NET patients.
KW - cytokines
KW - drug-resistance
KW - mTOR–mammalian target of rapamycin
KW - neuroendocrine tumors
KW - somatostatin analogs
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U2 - 10.3389/fonc.2020.01047
DO - 10.3389/fonc.2020.01047
M3 - Article
AN - SCOPUS:85088512079
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1047
ER -