title: CD86⁺/CD206⁺, Diametrically Polarized Tumor-Associated Macrophages, Predict Hepatocellular Carcinoma Patient Prognosis.
abstract: Tumor-associated macrophages (TAMs), the most abundant infiltrating immune cells in tumor microenvironment, have distinct functions in hepatocellular carcinoma (HCC) progression. CD68⁺ TAMs represent multiple polarized immune cells mainly containing CD86⁺ antitumoral M1 macrophages and CD206⁺ protumoral M2 macrophages. TAMs expression and density were assessed by immunohistochemical staining of CD68, CD86, and CD206 in tissue microarrays from 253 HCC patients. Clinicopathologic features and prognostic value of these markers were evaluated. We found that CD68⁺ TAMs were not associated with clinicopathologic characteristics and prognosis in HCC. Low presence of CD86⁺ TAMs and high presence of CD206⁺ TAMs were markedly correlated with aggressive tumor phenotypes, such as multiple tumor number and advanced tumor-node-metastasis (TNM) stage; and were associated with poor overall survival (OS) (p = 0.027 and p = 0.024, respectively) and increased time to recurrence (TTR) (p = 0.037 and p = 0.031, respectively). In addition, combined analysis of CD86 and CD206 provided a better indicator for OS (p = 0.011) and TTR (p = 0.024) in HCC than individual analysis of CD86 and CD206. Moreover, CD86⁺/CD206⁺ TAMs predictive model also had significant prognosis value in α-fetoprotein (AFP)-negative patients (OS: p = 0.002, TTR: p = 0.005). Thus, these results suggest that combined analysis of immune biomarkers CD86 and CD206 could be a promising HCC prognostic biomarker.
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 13211210002@fudan.edu.cn.|Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 13211210002@fudan.edu.cn.|Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 13211210002@fudan.edu.cn.
authors.forename: Pingping
authors.initials: P
authors.lastname: Dong
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 14211210033@fudan.edu.cn.|Department of Hepatic Surgery, Liver Cancer Institute, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China. 14211210033@fudan.edu.cn.
authors.forename: Lijie
authors.initials: L
authors.lastname: Ma
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 15111210063@fudan.edu.cn.|Department of Hepatic Surgery, Liver Cancer Institute, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Zhongshan Hospital, Fudan University, Shanghai 200032, China. 15111210063@fudan.edu.cn.
authors.forename: Longzi
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 14111210029@fudan.edu.cn.|Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 14111210029@fudan.edu.cn.|Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 14111210029@fudan.edu.cn.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. zhangsi_1@aliyun.com.
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. dong.ling@zs-hospital.sh.cn.|Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. dong.ling@zs-hospital.sh.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. xue.ruyi@zs-hospital.sh.cn.|Shanghai Institute of Liver Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China. xue.ruyi@zs-hospital.sh.cn.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Xue
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. shechen@fudan.edu.cn.
authors.forename: She
authors.initials: S
authors.lastname: Chen
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology*; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051940:B7-2 Antigen; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: AFP; CD206; CD86; hepatocellular carcinoma; prognosis; tumor-associated macrophages