Journal
ONCOTARGET
Volume 6, Issue 24, Pages 20204-20214Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3887
Keywords
tumor-infiltrating macrophages; CD204; CD169; urothelial cell carcinoma of the bladder (UCB)
Categories
Funding
- China Postdoctoral Science Foundation [2014M562241]
- National Natural Science Foundation of China [81402106, U1301221, 81472384, 81372729, 81372883, 81272808, 81172431, 81101935]
- Guangdong Province Natural Scientific Foundation [S2013020012671, 07117336, 10151008901000024]
- Specialized Research Fund for the Doctoral Program of Higher Education [20130171110073]
- Sun Yat-Sen University [2007018]
- Elite Young Scholars Program of Sun Yat-Sen Memorial Hospital [J201401]
- National Clinical Key Specialty Construcion Project for Department of Urology
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University [KLB09001]
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013] 163]
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Macrophages (M phi s) 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 M phi phenotypes in patients with urothelial cell carcinoma of the bladder (UCB), with a focus on M phi tissue microlocalization. M phi s were assessed by immunohistochemistry in tissues from 302 UCB patients using CD68 as a pan-M phi marker, and CD204 and CD169 as robust pro-and anti-tumoral M phi phenotype markers, respectively. Our data showed that these M phi 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(+) M phi s. Kaplan-Meier analysis revealed that all INT-and ST-infiltrating CD204(+) or CD169(+) M phi densities were inversely associated with overall survival (all P < 0.01). By multivariate analysis, ST-infiltrating CD204(+) M phi density emerged as an independent prognostic factor for overall survival (HR, 1.981; P = 0.022). Moreover, the density of ST-infiltrating CD204(+) M phi s 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(+) M phi s might play detrimental protumoral roles and represent the predominant M phi phenotype in human bladder cancer.
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