Activity and Functions of Tumor-associated Macrophages in Prostate Carcinogenesis

Matteo Santoni, Liang Cheng, Alessandro Conti, Cinzia Mariani, Antonio Lopez-Beltran, Rodolfo Montironi, Nicola Battelli

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4 Scopus citations

Abstract

Context: Tumor-associated macrophages (TAMs) constitute a heterogenous population and are highly represented in prostate cancer (PCa) primary tumor and metastases. Under various stimuli, macrophages can polarize into antitumoral M1 or protumoral M2 phenotypes. Objective: In this review, we will focus on the activity and functions of TAMs and associated molecules in PCa carcinogenesis, thus underling their potential as therapeutic targets in these patients. Evidence acquisition: To identify relevant studies, we performed a review of citations from PubMed from January 1966 to August 2017. The search was conducted by combining the words "macrophages" or "inflammation" to "prostate cancer." Data from ongoing trials were reported from clinicaltrials.gov. Evidence synthesis: TAMs and related molecules are implicated in PCa cell growth, survival, and migration. Furthermore, they are involved in PCa angiogenesis and in the development of bone metastases. Moreover, TAMs can regulate the expression of programmed cell death-1 and its ligand programmed death-ligand 1, thus representing an ideal candidate for targeted approaches in PCa patients. Based on these evidences, several TAM-centered strategies have been proposed and are in the course of investigation in PCa patients. These approaches include TAM re-education from M2 to M1 phenotype, the depletion of their number, and their use as vehicles for gene therapy. Conclusions: The pivotal role exerted by TAMs in PCa carcinogenesis and progression will open the way to the design of TAM-centered therapeutic approaches in these patients. This will represent a crucial step forward in increasing the efficacy of immunotherapy in patients with PCa. Tumor-associated macrophages (TAMs) are highly represented in prostate cancer (PCa) primary tumor and metastases. TAMs are implicated in PCa cell growth, survival, and migration, as well as being involved in PCa angiogenesis and in the development of bone metastases. Several TAM-centered strategies have been proposed and are in the course of investigation in PCa patients.

Original languageEnglish (US)
JournalEuropean Urology, Supplements
DOIs
StateAccepted/In press - 2017

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Keywords

  • Carcinogenesis
  • Inflammation
  • Prostate cancer
  • Tumor microenvironment
  • Tumor-associated macrophage

ASJC Scopus subject areas

  • Urology

Cite this

Santoni, M., Cheng, L., Conti, A., Mariani, C., Lopez-Beltran, A., Montironi, R., & Battelli, N. (Accepted/In press). Activity and Functions of Tumor-associated Macrophages in Prostate Carcinogenesis. European Urology, Supplements. https://doi.org/10.1016/j.eursup.2017.09.002