Prognostic Value of Polarized Macrophages in Patients with Hepatocellular Carcinoma After Curative Resection

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2016 Feb 5

PMID 26843477

Citations 27

Authors

Qing-Hua Shu

Yong-Sheng Ge

Hua-Xing Ma

Xiao-Qiang Gao

Jing-Jing Pan

Dong Liu

Ge-Liang Xu

Jin-Liang Ma

Wei-Dong Jia

Affiliations

Soon will be listed here.

Abstract

As the most predominant tumour-infiltrating immune cells, tumour-associated macrophages (TAMs) are significant for fostering tumour growth, progression and metastasis. CD68-positive TAMs display dissimilarly polarized programmes comprising CD11c-positive pro-inflammatory macrophages (M1) and CD206-positive immunosuppressive macrophages (M2). The aim of this study is to determine the prognostic significance of diametrically polarized TAMs in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values. This study included 80 consecutive patients with HCC, and we evaluated diametrically polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c and CD206. Prognostic values and clinicopathologic features were assessed in these patients. High versus low CD11c-positive TAM density (P = 0.005) and low versus high CD206-positive TAM density (P = 0.002) were associated with better overall survival, whereas CD68-positive TAM density had no prognostic significance (low versus high, P = 0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence-free survival (all P > 0.05). Multivariate Cox regression analysis identified CD11c-positive and CD206-positive TAMs as an independent prognostic factor (P < 0.001, P = 0.031, respectively). Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system.

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References

Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M . CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009; 15(8):914-20. DOI: 10.1038/nm.1964. View

Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, Sano K . Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology. 2008; 134(7):1908-16. DOI: 10.1053/j.gastro.2008.02.091. View

Senovilla L, Vacchelli E, Galon J, Adjemian S, Eggermont A, Fridman W . Trial watch: Prognostic and predictive value of the immune infiltrate in cancer. Oncoimmunology. 2012; 1(8):1323-1343. PMC: 3518505. DOI: 10.4161/onci.22009. View

Zhang Q, Liu L, Gong C, Shi H, Zeng Y, Wang X . Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One. 2013; 7(12):e50946. PMC: 3532403. DOI: 10.1371/journal.pone.0050946. View

Forner A, Llovet J, Bruix J . Hepatocellular carcinoma. Lancet. 2012; 379(9822):1245-55. DOI: 10.1016/S0140-6736(11)61347-0. View

Biswas S, Mantovani A . Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010; 11(10):889-96. DOI: 10.1038/ni.1937. View

Sica A, Mantovani A . Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012; 122(3):787-95. PMC: 3287223. DOI: 10.1172/JCI59643. View

Xu L, Zhu Y, Chen L, An H, Zhang W, Wang G . Prognostic value of diametrically polarized tumor-associated macrophages in renal cell carcinoma. Ann Surg Oncol. 2014; 21(9):3142-50. DOI: 10.1245/s10434-014-3601-1. View

Cho K, Miyoshi H, Kuroda S, Yasuda H, Kamiyama K, Nakagawara J . The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery. J Stroke Cerebrovasc Dis. 2013; 22(7):910-8. DOI: 10.1016/j.jstrokecerebrovasdis.2012.11.020. View

10.

Weber M, Moebius P, Buttner-Herold M, Amann K, Preidl R, Neukam F . Macrophage polarisation changes within the time between diagnostic biopsy and tumour resection in oral squamous cell carcinomas--an immunohistochemical study. Br J Cancer. 2015; 113(3):510-9. PMC: 4522624. DOI: 10.1038/bjc.2015.212. View

11.

Erreni M, Mantovani A, Allavena P . Tumor-associated Macrophages (TAM) and Inflammation in Colorectal Cancer. Cancer Microenviron. 2011; 4(2):141-54. PMC: 3170420. DOI: 10.1007/s12307-010-0052-5. View

12.

Ding P, Wang W, Wang J, Yang Z, Xue L . Expression of tumor-associated macrophage in progression of human glioma. Cell Biochem Biophys. 2014; 70(3):1625-31. DOI: 10.1007/s12013-014-0105-3. View

13.

Forssell J, Oberg A, Henriksson M, Stenling R, Jung A, Palmqvist R . High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res. 2007; 13(5):1472-9. DOI: 10.1158/1078-0432.CCR-06-2073. View

14.

McShane L, Altman D, Sauerbrei W, Taube S, Gion M, Clark G . REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005; 93(4):387-91. PMC: 2361579. DOI: 10.1038/sj.bjc.6602678. View

15.

Grivennikov S, Greten F, Karin M . Immunity, inflammation, and cancer. Cell. 2010; 140(6):883-99. PMC: 2866629. DOI: 10.1016/j.cell.2010.01.025. View

16.

Mantovani A, Locati M, Vecchi A, Sozzani S, Allavena P . Decoy receptors: a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol. 2001; 22(6):328-36. DOI: 10.1016/s1471-4906(01)01941-x. View

17.

Ohno S, Ohno Y, Suzuki N, Kamei T, Koike K, Inagawa H . Correlation of histological localization of tumor-associated macrophages with clinicopathological features in endometrial cancer. Anticancer Res. 2004; 24(5C):3335-42. View

18.

Karnevi E, Andersson R, Rosendahl A . Tumour-educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion. Immunol Cell Biol. 2014; 92(6):543-52. DOI: 10.1038/icb.2014.22. View

19.

Martinez-Pomares L . The mannose receptor. J Leukoc Biol. 2012; 92(6):1177-86. DOI: 10.1189/jlb.0512231. View

20.

Billiau A, Matthys P . Interferon-gamma: a historical perspective. Cytokine Growth Factor Rev. 2009; 20(2):97-113. DOI: 10.1016/j.cytogfr.2009.02.004. View