title: High CD204+ tumor-infiltrating macrophage density predicts a poor prognosis in patients with urothelial cell carcinoma of the bladder.
abstract: Macrophages (Mφs) are a major cell type that can infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. This study attempted to investigate the prognostic values of various tumor-infiltrating Mφ phenotypes in patients with urothelial cell carcinoma of the bladder (UCB), with a focus on Mφ tissue microlocalization. Mφs were assessed by immunohistochemistry in tissues from 302 UCB patients using CD68 as a pan-Mφ marker, and CD204 and CD169 as robust pro- and anti-tumoral Mφ phenotype markers, respectively. Our data showed that these Mφ phenotypes were predominately distributed in stromal (ST) rather than in intratumoral (INT) regions (all P < 0.0001). Surprisingly, CD204 and CD169 can be co-expressed by the same CD68+ Mφs. Kaplan-Meier analysis revealed that all INT- and ST-infiltrating CD204+ or CD169+ Mφ densities were inversely associated with overall survival (all P < 0.01). By multivariate analysis, ST-infiltrating CD204+ Mφ density emerged as an independent prognostic factor for overall survival (HR, 1.981; P = 0.022). Moreover, the density of ST-infiltrating CD204+ Mφs was positively associated with the tumor size (P = 0.001), tumor stage (P < 0.0001), nodal metastasis (P < 0.0001), and histological grade (P < 0.0001). Our findings suggest that CD204+ Mφs might play detrimental protumoral roles and represent the predominant Mφ phenotype in human bladder cancer.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, PR China.|Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Shaoxu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhongshan) University, Guangzhou, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Urology, Cancer Center, Sun Yat-Sen (Zhongshan) University, Guangzhou, PR China.
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Wan
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen (Zhongshan) University, Guangzhou, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, PR China.|Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen (Zhosngshan) University, Guangzhou, PR China.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis / Q000276:immunology*; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: C495139:MSR1 protein, human; D051117:Scavenger Receptors, Class A
keywords: CD169; CD204; tumor-infiltrating macrophages; urothelial cell carcinoma of the bladder (UCB)