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Immunologic Research
Published in: Immunologic Research 4-5/2019

01-10-2019 | Glioma | Original Article

The sialoglycan-Siglec-E checkpoint axis in dexamethasone-induced immune subversion in glioma-microglia transwell co-culture system

Authors: Przemyslaw Wielgat, Robert Czarnomysy, Emil Trofimiuk, Halina Car

Published in: Immunologic Research | Issue 4-5/2019

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Abstract

Dexamethasone (Dex) is considered as the main steroid routinely used in the standard therapy of brain tumor-induced edema. Strong immunosuppressive effects of Dex on effector systems of the immune system affect the patients’ antitumor immunity and may thereby worsen the prognosis. Siglecs and their interacting sialoglycans have been described as a novel glyco-immune checkpoint axis that promotes cancer immune evasion. Despite the aberrant glycosylation in cancer is described, mechanisms involved in regulation of immune checkpoints in gliomas are not fully understood. The aim of this study was to investigate the effect of Dex on the Siglec-sialic acid interplay and determine its significance in immune inversion in monocultured and co-cultured microglia and glioma cells. Both monocultured and co-cultured in transwell system embryonic stem cell-derived microglia (ESdM) and glioma GL261 cells were exposed to Dex. Cell viability, immune inversion markers, and interaction between sialic acid and Siglec-E were detected by flow cytometry. Cell invasion was analyzed by scratch-wound migration assay using inverted phase-contrast microscopy. Exposure to Dex led to significant changes in IL-1β, IL-10, Iba-1, and Siglec-E in co-cultured microglia compared to naïve or monocultured cells. These alterations were accompanied by increased α2.8-sialylation and Siglec-E fusion protein binding to co-cultured glioma cell membranes. This study suggests that the interplay between sialic acids and Siglecs is a sensitive immune checkpoint axis and may be crucial for Dex-induced dampening of antitumor immunity. The targeting of sialic acid-Siglec glyco-immune checkpoint can be a novel therapeutic method in glioma therapy.
Literature
1.
Bosma I, Reijneveld JC, Douw L, Vos MJ, Postma TJ, Aaronson NK, et al. Health-related quality of life of long-term high-grade glioma survivors. Neuro-Oncology. 2009;11:51–8.PubMedPubMedCentral
2.
3.
Yan D, Kowal J, Akkari L, Schuhmacher AJ, Huse JT, West BL, et al. Inhibition of colony stimulating factor-1 receptor abrogates microenvironment-mediated therapeutic resistance in gliomas. Oncogene. 2017;36:6049–58.PubMedPubMedCentral
4.
5.
Vajaria BN, Patel KR, Begum R, Patel PS. Sialylation: an avenue to target cancer cells. Pathol. Oncol. Res. 2016;22:443–7.PubMed
6.
7.
8.
Mingari MC, Vitale C, Romagnani C, Falco M, Moretta L. p75/AIRM1 and CD33, two sialoadhesin receptors that regulate the proliferation or the survival of normal and leukemic myeloid cells. Immunol. Rev. 2001;181:260–8.PubMed
9.
Steinke JW, Liu L, Huyett P, Negri J, Payne SC, Borish L. Prominent role of IFN-γ in patients with aspirin-exacerbated respiratory disease. J. Allergy Clin. Immunol. 2013;132:856–65.PubMedPubMedCentral
10.
Wielgat P, Mroz RM, Stasiak-Barmuta A, Szepiel P, Chyczewska E, Braszko JJ, et al. Inhaled corticosteroids increase siglec-5/14 expression in sputum cells of COPD patients. Adv. Exp. Med. Biol. 2015;839:1–5.PubMed
11.
Wielgat P, Trofimiuk E, Czarnomysy R, Braszko JJ, Car H. Sialic acids as cellular markers of immunomodulatory action of dexamethasone on glioma cells of different immunogenicity. Mol. Cell. Biochem. 2019;455:147–57.PubMed
12.
Pitter KL, Tamagno I, Alikhanyan K, Hosni-Ahmed A, Pattwell SS, Donnola S, et al. Corticosteroids compromise survival in glioblastoma. Brain. 2016;139:1458–71.PubMedPubMedCentral
13.
14.
Shields LB, Shelton BJ, Shearer AJ, Chen L, Sun DA, Parsons S, et al. Dexamethasone administration during definitive radiation and temozolomide renders a poor prognosis in a retrospective analysis of newly diagnosed glioblastoma patients. Radiat. Oncol. 2015;10:222.PubMedPubMedCentral
15.
Wong ET, Lok E, Gautam S, Swanson KD. Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma. Br. J. Cancer. 2015;113:232–41.PubMedPubMedCentral
16.
Napoli I, Kierdorf K, Neumann H. Microglial precursors derived from mouse embryonic stem cells. Glia. 2009;57:1660–71.PubMed
17.
Rezonja K, Sostaric M, Vidmar G, Mars T. Dexamethasone produces dose-dependent inhibition of sugammadex reversal in in vitro innervated primary human muscle cells. Anesth. Analg. 2014;118:755–63.PubMed
18.
Goya L, Feng PT, Aliabadi S, Timiras PS. Effect of growth factors on the in vitro growth and differentiation of early and late passage C6 glioma cells. Int. J. Dev. Neurosci. 1996;14:409–17.PubMed
19.
Batash R, Asna N, Schaffer P, Francis N, Schaffer M. Glioblastoma multiforme, diagnosis and treatment; recent literature review. Curr. Med. Chem. 2017;24:3002–9.PubMed
20.
Adams OJ, Stanczak MA, von Gunten S, Läubli H. Targeting sialic acid-Siglec interactions to reverse immune suppression in cancer. Glycobiology. 2018;28:640–7.PubMed
21.
Pearce OM, Läubli H. Sialic acids in cancer biology and immunity. Glycobiology. 2016;26:111–28.PubMed
22.
Amoureux MC, Coulibaly B, Chinot O, Loundou A, Metellus P, Rougon G, et al. Polysialic acid neural cell adhesion molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines. BMC Cancer. 2010;10:1–12.
23.
Petridis AK, Wedderkopp H, Hugo HH, Maximilian MH. Polysialic acid overexpression in malignant astrocytomas. Acta Neurochir. 2009;15:601–4.
24.
Monzo HJ, Coppieters N, Park TIH, Dieriks BV, Faull RLM, Dragunow M, et al. Insulin promotes cell migration by regulating PSA-NCAM. Exp. Cell Res. 2017;355:26–39.PubMed
25.
Beatson R, Tajadura-Ortega V, Achkova D, Picco G, Tsourouktsoglou TD, Klausing S, et al. The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9. Nat. Immunol. 2016;17:1273–81.PubMedPubMedCentral
26.
Läubli H, Pearce OM, Schwarz F, Siddiqui SS, Deng L, Stanczak MA, et al. Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer. Proc. Natl. Acad. Sci. U. S. A. 2014;111:14211–6.PubMedPubMedCentral
27.
Haas Q, Boligan KF, Jandus C, Schneider C, Simillion C, Stanczak MA, et al. Siglec-9 regulates an effector memory CD8+ T-cell subset that congregates in the melanoma tumor microenvironment. Cancer Immunol Res. 2019;7:707–18.PubMed
28.
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, et al. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat. Med. 2019;25:656–66.PubMedPubMedCentral
29.
30.
31.
Salminen A, Kaarniranta K. Siglec receptors and hiding plaques in Alzheimer's disease. J Mol Med (Berl). 2009;87:697–701.PubMed
32.
Luedi MM, Singh SK, Mosley JC, Hatami M, Gumin J, Sulman EP, et al. A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients. J. Neurosurg. Anesthesiol. 2017;29:46–58.PubMedPubMedCentral
33.
Rouiller Y, Périlleux A, Marsaut M, Stettler M, Vesin MN, Broly H. Effect of hydrocortisone on the production and glycosylation of an Fc-fusion protein in CHO cell cultures. Biotechnol. Prog. 2012;28:803–13.PubMed
34.
Burkhardt T, Lüdecke D, Spies L, Wittmann L, Westphal M, Flitsch J. Hippocampal and cerebellar atrophy in patients with Cushing’s disease. Neurosurg. Focus. 2015;39:E5.PubMed
35.
Zhang H, Zhao Y, Wang Z. Chronic corticosterone exposure reduces hippocampal astrocyte structural plasticity and induces hippocampal atrophy in mice. Neurosci. Lett. 2015;592:76–81.PubMed
36.
Wielgat P, Walesiuk A, Braszko JJ. Effects of chronic stress and corticosterone on sialidase activity in the rat hippocampus. Behav. Brain Res. 2011;222:363–7.PubMed
37.
Zeng Z, Li M, Wang M, Wu X, Li Q, Ning Q, et al. Increased expression of Siglec-9 in chronic obstructive pulmonary disease. Sci. Rep. 2017;7:10116.PubMedPubMedCentral
38.
Angata T, Ishii T, Motegi T, Oka R, Taylor RE, Soto PC, et al. Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell. Mol. Life Sci. 2013;70:3199–4010.PubMedPubMedCentral
39.
Genin M, Clement F, Fattaccioli A, Raes M, Michiels C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer. 2015;15:577.PubMedPubMedCentral
40.
Pepe G, De Maglie M, Minoli L, Villa A, Maggi A, Vegeto E. Selective proliferative response of microglia to alternative polarization signals. J. Neuroinflammation. 2017;14:236.PubMedPubMedCentral
41.
Gjorgjevski M, Hannen R, Carl B, Li Y, Landmann E, Buchholz M, Bartsch JW, Nimsky C. Molecular profiling of the tumor microenvironment in glioblastoma patients: correlation of microglia/macrophage polarization state with metalloprotease expression profiles and survival. Biosci. Rep. 2019;39: pii:BSR20182361.
42.
Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 2016;53:1181–94.PubMed
43.
Quatromoni JG, Eruslanov E. Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer. Am. J. Transl. Res. 2012;4:376–89.PubMedPubMedCentral
44.
Tedesco S, Bolego C, Toniolo A, Nassi A, Fadini GP, Locati M, et al. Phenotypic activation and pharmacological outcomes of spontaneously differentiated human monocyte-derived macrophages. Immunobiology. 2015;220:545–54.PubMed
45.
Lübbers J, Rodríguez E, van Kooyk Y. Modulation of immune tolerance via Siglec-sialic acid interactions. Front. Immunol. 2018;9:2807.PubMedPubMedCentral
46.
Graeber MB, Scheithauer BW, Kreutzberg GW. Microglia in brain tumors. Glia. 2002;40:252–9.PubMed
47.
Roggendorf W, Strupp S, Paulus W. Distribution and characterization of microglia/macrophages in human brain tumors. Acta Neuropathol. 1996;92:288–93.PubMed
48.
Santegoets KCM, Gielen PR, Büll C, Schulte BM, Kers-Rebel ED, Küsters B, et al. Expression profiling of immune inhibitory Siglecs and their ligands in patients with glioma. Cancer Immunol. Immunother. 2019;68:937–49.PubMedPubMedCentral
Metadata
Title
The sialoglycan-Siglec-E checkpoint axis in dexamethasone-induced immune subversion in glioma-microglia transwell co-culture system
Authors
Przemyslaw Wielgat
Robert Czarnomysy
Emil Trofimiuk
Halina Car
Publication date
01-10-2019
Publisher
Springer US
Published in
Immunologic Research / Issue 4-5/2019
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-019-09106-7

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