J Neurol Surg A Cent Eur Neurosurg 2018; 79(02): 159-162
DOI: 10.1055/s-0037-1603949
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Immune Pathobiology of Schwannomas: A Concise Review

İlhan Elmaci
1   Neuroacademy Group, Sisli, Istanbul, Turkey
,
Meric A. Altinoz
1   Neuroacademy Group, Sisli, Istanbul, Turkey
2   Department of Neurosurgery, Memorial Health Group, Istanbul, Turkey
,
Ramazan Sari
1   Neuroacademy Group, Sisli, Istanbul, Turkey
› Institutsangaben
Weitere Informationen

Publikationsverlauf

05. Dezember 2016

05. April 2017

Publikationsdatum:
08. November 2017 (online)

Abstract

Schwannomas are benign tumors treatable with neurosurgery or radiosurgery, yet a small subset may exhibit aggressive growth. Hence illuminating their immune features can help develop better treatments. A tumor-promoting inflammation exists in schwannomas. Transcription factor NF-κB triggers synthesis of inflammatory cytokines and chemokines. NF-κB is suppressed by NF2/merlin, yet it is mutated or repressed in schwannomas, and therefore MCP-1/CCL2, MIP-1α/CCL3, CXCL16, and CXCR6/Bonzo are likely expressed in these tumors. CD68+ and CD163+ macrophages may infiltrate schwannomas and promote their growth. Anti-inflammatory salicylates inhibit schwannomas in cell culture and clinically. Schwannomas that cannot be completely removed by neurosurgery or controlled by radiosurgery may be suitable targets of pharmacologic interventions focusing on immune mechanisms.

 
  • References

  • 1 Held-Feindt J, Rehmke B, Mentlein R. , et al. Overexpression of CXCL16 and its receptor CXCR6/Bonzo promotes growth of human schwannomas. Glia 2008; 56 (07) 764-774
  • 2 Mori K, Chano T, Yamamoto K, Matsusue Y, Okabe H. Expression of macrophage inflammatory protein-1alpha in Schwann cell tumors. Neuropathology 2004; 24 (02) 131-135
  • 3 de Vries M, Hogendoorn PC, Briaire-de Bruyn I, Malessy MJ, van der Mey AG. Intratumoral hemorrhage, vessel density, and the inflammatory reaction contribute to volume increase of sporadic vestibular schwannomas. Virchows Arch 2012; 460 (06) 629-636
  • 4 Dilwali S, Kao SY, Fujita T, Landegger LD, Stankovic KM. Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas. Transl Res 2015; 166 (01) 1-11
  • 5 de Vries M, Briaire-de Bruijn I, Malessy MJ, de Bruïne SF, van der Mey AG, Hogendoorn PC. Tumor-associated macrophages are related to volumetric growth of vestibular schwannomas. Otol Neurotol 2013; 34 (02) 347-352
  • 6 Pekmezci M, Reuss DE, Hirbe AC. , et al. Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. Mod Pathol 2015; 28 (02) 187-200
  • 7 Naghshineh H, Shahin D, Sahraian MA, Minagar A. Co-existence of neurofibromatosis type 2 and multiple sclerosis: a case report. Mult Scler Relat Disord 2014; 3 (03) 384-386
  • 8 Stemmer-Rachamimov AO, Xu L, Gonzalez-Agosti C. , et al. Universal absence of merlin, but not other ERM family members, in schwannomas. Am J Pathol 1997; 151 (06) 1649-1654
  • 9 Kim JY, Kim H, Jeun SS. , et al. Inhibition of NF-kappaB activation by merlin. Biochem Biophys Res Commun 2002; 296 (05) 1295-1302
  • 10 Altinoz MA, Korkmaz R. NF-kappaB, macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer. Neoplasma 2004; 51 (04) 239-247
  • 11 Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol 1993; 52 (02) 106-113
  • 12 Gering KM, Marx JA, Lennartz K, Fischer C, Rajewsky MF, Kindler-Röhrborn A. The interaction mode of premalignant Schwann and immune effector cells during chemically induced carcinogenesis in the rat peripheral nervous system is strongly influenced by genetic background. Cancer Res 2006; 66 (09) 4708-4714
  • 13 Xia L, Zhang H, Yu C. , et al. Fluid-fluid level in cystic vestibular schwannoma: a predictor of peritumoral adhesion. J Neurosurg 2014; 120 (01) 197-206
  • 14 Mechtersheimer G, Staudter M, Möller P. Expression of the natural killer cell-associated antigens CD56 and CD57 in human neural and striated muscle cells and in their tumors. Cancer Res 1991; 51 (04) 1300-1307
  • 15 Kang S, Yang C, Luo R. LysoPtdOH enhances CXCL16 production stimulated by LPS from macrophages and regulates T cell migration. Lipids 2008; 43 (11) 1075-1083
  • 16 Lehrke M, Millington SC, Lefterova M. , et al. CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humans. J Am Coll Cardiol 2007; 49 (04) 442-449
  • 17 Chalabi-Dchar M, Cassant-Sourdy S, Duluc C. , et al. Loss of somatostatin receptor subtype 2 promotes growth of KRAS-induced pancreatic tumors in mice by activating PI3K signaling and overexpression of CXCL16. Gastroenterology 2015; 148 (07) 1452-1465
  • 18 McCarty MF, Block KI. Preadministration of high-dose salicylates, suppressors of NF-kappaB activation, may increase the chemosensitivity of many cancers: an example of proapoptotic signal modulation therapy. Integr Cancer Ther 2006; 5 (03) 252-268
  • 19 Kandathil CK, Dilwali S, Wu CC. , et al. Aspirin intake correlates with halted growth of sporadic vestibular schwannoma in vivo. Otol Neurotol 2014; 35 (02) 353-357
  • 20 Li W, You L, Cooper J. , et al. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell 2010; 140 (04) 477-490
  • 21 Ren W, Shen S, Sun Z. , et al. Jak-STAT3 pathway triggers DICER1 for proteasomal degradation by ubiquitin ligase complex of CUL4A(DCAF1) to promote colon cancer development. Cancer Lett 2016; 375 (02) 209-220
  • 22 Andersen V, Vogel U. Systematic review: interactions between aspirin, and other nonsteroidal anti-inflammatory drugs, and polymorphisms in relation to colorectal cancer. Aliment Pharmacol Ther 2014; 40 (02) 147-159
  • 23 Li P, Wu H, Zhang H. , et al. Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis. Gut 2015; 64 (09) 1419-1425
  • 24 Wang Y, Zhang FC, Wang YJ. The efficacy and safety of non-steroidal anti-inflammatory drugs in preventing the recurrence of colorectal adenoma: a meta-analysis and systematic review of randomized trials. Colorectal Dis 2015; 17 (03) 188-196
  • 25 Rustgi AK, Xu L, Pinney D. , et al. Neurofibromatosis 2 gene in human colorectal cancer. Cancer Genet Cytogenet 1995; 84 (01) 24-26
  • 26 Cačev T, Aralica G, Lončar B, Kapitanović S. Loss of NF2/Merlin expression in advanced sporadic colorectal cancer. Cell Oncol (Dordr) 2014; 37 (01) 69-77
  • 27 Agnihotri S, Jalali S, Wilson MR. , et al. The genomic landscape of schwannoma. Nat Genet 2016; 48 (11) 1339-1348
  • 28 Pan MR, Hung WC. Nonsteroidal anti-inflammatory drugs inhibit matrix metalloproteinase-2 via suppression of the ERK/Sp1-mediated transcription. J Biol Chem 2002; 277 (36) 32775-32780
  • 29 Abiru S, Nakao K, Ichikawa T. , et al. Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma cells. Hepatology 2002; 35 (05) 1117-1124
  • 30 Cusimano A, Foderà D, D'Alessandro N. , et al. Potentiation of the antitumor effects of both selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatic cancer cells by inhibition of the MEK/ERK pathway. Cancer Biol Ther 2007; 6 (09) 1461-1468
  • 31 Gao J, Niwa K, Takemura M. , et al. Significant anti-proliferation of human endometrial cancer cells by combined treatment with a selective COX-2 inhibitor NS398 and specific MEK inhibitor U0126. Int J Oncol 2005; 26 (03) 737-744
  • 32 Sun Y, Sinicrope FA. Selective inhibitors of MEK1/ERK44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells. Mol Cancer Ther 2005; 4 (01) 51-59