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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas

Authors: Chanhee Lee, Joongyub Lee, Seung Ah Choi, Seung-Ki Kim, Kyu-Chang Wang, Sung-Hye Park, Se Hoon Kim, Ji Yeoun Lee, Ji Hoon Phi

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Recent progress in molecular analysis has advanced the understanding of medulloblastoma (MB) and is anticipated to facilitate management of the disease. MB is composed of 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Macrophages play a crucial role in the tumor microenvironment; however, the functional role of their activated phenotype (M1/M2) remains controversial. Herein, we investigate the correlation between tumor-associated macrophage (TAM) recruitment within the MB subgroups and prognosis.

Methods

Molecular subgrouping was performed by a nanoString-based RNA assay on retrieved snap-frozen tissue samples. Immunohistochemistry (IHC) and immunofluorescence (IF) assays were performed on subgroup identified samples, and the number of polarized macrophages was quantified from IHC. Survival analyses were conducted on collected clinical data and quantified macrophage data.

Results

TAM (M1/M2) recruitment in SHH MB was significantly higher compared to that in other subgroups. A Kaplan-Meier survival curve and multivariate Cox regression demonstrated that high M1 expressers showed worse overall survival (OS) and progression-free survival (PFS) than low M1 expressers in SHH MB, with relative risk (RR) values of 11.918 and 6.022, respectively.

Conclusion

M1 rather than M2 correlates more strongly with worse outcome in SHH medulloblastoma.
Appendix
Available only for authorised users
Literature
1.
RM DS, Jones BR, Lowis SP, Kurian KM. Pediatric medulloblastoma - update on molecular classification driving targeted therapies. Front Oncol. 2014;176(4).
2.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20.CrossRefPubMed
3.
Margol AS, Robison NJ, Gnanachandran J, Hung LT, Kennedy RJ, Vali M, Dhall G, Finlay JL, Erdreich-Epstein A, Krieger MD, et al. Tumor-associated macrophages in SHH subgroup of medulloblastomas. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015;21(6):1457–65.CrossRef
4.
Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123(4):465–72.CrossRefPubMed
5.
Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, Cho YJ, Koster J, Schouten-van Meeteren A, van Vuurden D, et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3, and group 4 medulloblastomas. Acta Neuropathol. 2012;123(4):473–84.CrossRefPubMedPubMedCentral
6.
Northcott PA, Shih DJ, Remke M, Cho YJ, Kool M, Hawkins C, Eberhart CG, Dubuc A, Guettouche T, Cardentey Y, et al. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol. 2012;123(4):615–26.CrossRefPubMed
7.
Triscott J, Lee C, Foster C, Manoranjan B, Pambid MR, Berns R, Fotovati A, Venugopal C, O'Halloran K, Narendran A, et al. Personalizing the treatment of pediatric medulloblastoma: polo-like kinase 1 as a molecular target in high-risk children. Cancer Res. 2013;73(22):6734–44.CrossRefPubMed
8.
Griesinger AM, Birks DK, Donson AM, Amani V, Hoffman LM, Waziri A, Wang M, Handler MH, Foreman NK. Characterization of distinct immunophenotypes across pediatric brain tumor types. J Immunol. 2013;191(9):4880–8.CrossRefPubMed
9.
Kennedy BC, Showers CR, Anderson DE, Anderson L, Canoll P, Bruce JN, Anderson RC. Tumor-associated macrophages in glioma: friend or foe? J. Oncol. 2013;2013:486912.CrossRefPubMedPubMedCentral
10.
Komohara Y, Ohnishi K, Kuratsu J, Takeya M. Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J Pathol. 2008;216(1):15–24.CrossRefPubMed
11.
Herrera M, Herrera A, Dominguez G, Silva J, Garcia V, Garcia JM, Gomez I, Soldevilla B, Munoz C, Provencio M, et al. Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer Sci. 2013;104(4):437–44.CrossRefPubMed
12.
Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P, Mantovani A. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008;18(5):349–55.CrossRefPubMed
13.
Almatroodi SA, McDonald CF, Darby IA, Pouniotis DS. Characterization of M1/M2 tumour-associated macrophages (TAMs) and Th1/Th2 cytokine profiles in patients with NSCLC. Cancer Microenviron. 2016;9(1):1–11.CrossRefPubMed
14.
15.
16.
17.
Zhang M, He Y, Sun X, Li Q, Wang W, Zhao A, Di W. A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. Journal of ovarian research. 2014;7:19.CrossRefPubMedPubMedCentral
18.
Squadrito ML, De Palma M. A niche role for periostin and macrophages in glioblastoma. Nat Cell Biol. 2015;17(2):107–9.CrossRefPubMed
19.
Barros MH, Hassan R, Niedobitek G. Tumor-associated macrophages in pediatric classical Hodgkin lymphoma: association with Epstein-Barr virus, lymphocyte subsets, and prognostic impact. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012;18(14):3762–71.CrossRef
20.
Williams CB, Yeh ES, Soloff AC. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy. NPJ breast cancer. 2016;2
21.
22.
Lee JY, Moon YJ, Lee HO, Park AK, Choi SA, Wang KC, Han JW, Joung JG, Kang HS, Kim JE, et al. Deregulation of Retinaldehyde dehydrogenase 2 leads to defective Angiogenic function of endothelial Colony-forming cells in pediatric Moyamoya disease. Arterioscler Thromb Vasc Biol. 2015;35(7):1670–7.CrossRefPubMed
23.
Wang XL, Jiang JT, Wu CP. Prognostic significance of tumor-associated macrophage infiltration in gastric cancer: a meta-analysis. Genetics and molecular research : GMR. 2016;15(4)
24.
Mei J, Xiao Z, Guo C, Pu Q, Ma L, Liu C, Lin F, Liao H, You Z, Liu L. Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: a systemic review and meta-analysis. Oncotarget. 2016;7(23):34217–28.CrossRefPubMedPubMedCentral
25.
Edin S, Wikberg ML, Dahlin AM, Rutegard J, Oberg A, Oldenborg PA, Palmqvist R. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PLoS One. 2012;7(10):e47045.CrossRefPubMedPubMedCentral
26.
Van Overmeire E, Laoui D, Keirsse J, Van Ginderachter JA, Sarukhan A. Mechanisms driving macrophage diversity and specialization in distinct tumor microenvironments and parallelisms with other tissues. Front Immunol. 2014;5:127.CrossRefPubMedPubMedCentral
27.
Haag D, Zipper P, Westrich V, Karra D, Pfleger K, Toedt G, Blond F, Delhomme N, Hahn M, Reifenberger J, et al. Nos2 inactivation promotes the development of medulloblastoma in Ptch1(+/−) mice by deregulation of Gap43-dependent granule cell precursor migration. PLoS Genet. 2012;8(3):e1002572.CrossRefPubMedPubMedCentral
28.
Wang J, Lin W, Popko B, Campbell IL. Inducible production of interferon-gamma in the developing brain causes cerebellar dysplasia with activation of the sonic hedgehog pathway. Mol Cell Neurosci. 2004;27(4):489–96.CrossRefPubMed
Metadata
Title
M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas
Authors
Chanhee Lee
Joongyub Lee
Seung Ah Choi
Seung-Ki Kim
Kyu-Chang Wang
Sung-Hye Park
Se Hoon Kim
Ji Yeoun Lee
Ji Hoon Phi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4457-8

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