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.

CD20+ tumor‐infiltrating immune cells and CD204+ M2 macrophages are associated with prognosis in thymic carcinoma

“…Furthermore, tumor‐infiltrating M2 macrophages were associated with poor treatment outcomes in renal cell carcinoma, melanoma, leiomyosarcoma and follicular lymphoma 42,43 . Among several markers for macrophages, CD204‐expressing M2 macrophages were prognostic factors in urothelial cell carcinoma of the bladder, esophageal squamous cell carcinoma, pancreatic cancer and NSCLC 44–47 . We observed a similar tendency of prognosis, indicating the importance of CD204 + M2 macrophages in the TME.…”

Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization

“…Class A1 scavenger receptor (SR-A1; also known as MSR1 and CD204) is a pattern recognition receptor involved in the progression of multiple tumors [6, 7, 14]. It is a marker for alternatively activated macrophages/microglia in glioma progression [15].…”

ANXA10 induction by interaction with tumor‐associated macrophages promotes the growth of esophageal squamous cell carcinoma

“…We demonstrated an association between an increased number of infiltrating CD204 + TAMs and the poor prognosis of ESCCs . CD204 + TAMs have been reported to correlate with poor prognosis in many cancers, including lung cancer, bladder cancer, breast cancer, ovarian cancer and uterine cervical adenocarcinoma . However, the pathological mechanisms of TAMs on the tumor microenvironment of ESCC remain unclear.…”