Increased tumor-associated macrophages in the prostate cancer microenvironment predicted patients' survival and responses to androgen deprivation therapies in Indonesian patients cohort

Background: Tumor-associated macrophages (TAMs) and microvessel density (MVD) play an essential
role for tumor progression in prostate cancer (PCa). In this study, we evaluated the association between
TAMs, the infiltration with tumor angiogenesis and the response to androgen deprivation therapies
(ADTs) in PCa to evaluate TAM infiltration as a predictive factor for PCa survival.
Materials and methods: Fifty-four specimens were collected and stained with CD 68 antibody to
investigated TAM infiltration in tumor. Von Willebrand factor was stained to evaluate MVD around the
cancer foci. We assessed the association between patient's age, preoperative serum prostate-specific
antigen, pathologic Gleason sum (GS), TAM infiltration, MVD, and the response to ADT for 5 years after
PCa diagnosis.
Results: The median TAM was observed in 28 (6-76)/high power field (x400). Increasing TAM correlated
with increasing tumor angiogenesis (P < 0.001, r ¼ 0.61), and the response to ADT was significantly better
in patients with fewer TAMs (<28) than in patients with higher TAMs (>28) (P ¼ 0.003). TAM infiltration
was significantly higher in those with higher serum prostate-specific antigen, higher GS, and metastasis.
Multivariate analysis showed that GS, ADT type, and MVD number were significant prognostic factors for
response to ADT in PCa (P < 0.0001). An increased infiltration of TAM [hazards ratio (HR) ¼ 4.47; 95%
confidence interval (CI): 1.97e10.15], MVD (HR ¼ 2.66; 95% CI: 1.27e5.61), metastatic status (HR ¼ 2.29;
95% CI: 0.14-0.60), and prostate volume (HR ¼ 2.19; 95% CI: 1.27e3.12) significantly correlated with
shorter survival in PCa patients by univariate analysis (P < 0.05). Multivariate analyses revealed that TAM
and metastatic status significantly correlated with poor overall survival.
Conclusions: TAMinfiltration is associated with response toADTand increased tumorangiogenesis in PCa.
GS, ADT type, andMVD in PCa specimens are useful predictive factors for poor response to ADT. Increasing
TAM and positive metastatic status were prognostic factors for a poorer survival in PCa patients.