Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients

J Immunol Methods. 2009 Aug 31;348(1-2):9-17. doi: 10.1016/j.jim.2009.06.004. Epub 2009 Jun 22.

Abstract

Introduction: Our goal was to study the hormonal regulation of immune cell infiltration in prostate cancer patients treated by androgen deprivation therapy (ADT) using an optimized computer-assistance quantification approach.

Methods: The relative density of immune cell subtypes (CD3(+), CD8(+), CD20(+), CD56(+), CD68(+) and Foxp3(+)) was analyzed by immunohistochemistry in archived prostate specimens from control patients (radical prostatectomy only, n=40) and ADT-treated patients (ADT prior to radical prostatectomy, n=35) using an image analysis software and a whole-slide scanner.

Results: ADT-treated patients had significantly increased relative density of CD3(+) (p<0.001) and CD8(+) T lymphocytes (p<0.001) as well as CD68(+) macrophages (p<0.001). Elevated abundance of CD56(+) Natural Killer (NK) cells was associated with a lower risk of prostate cancer progression (p=0.044), while a high density of CD68(+) macrophages was related to an increased risk of biochemical recurrence (p=0.011).

Conclusions: Our results demonstrate that the infiltration of specific immune cell subtypes is modulated by ADT. Furthermore our data confirm that NK cells have a protective role against tumor progression while macrophages seem to favor the development of advanced prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Androgens / immunology
  • Androgens / metabolism
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Cyproterone / therapeutic use
  • Flutamide / therapeutic use
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Leuprolide / therapeutic use
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Neoplasm Recurrence, Local / immunology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Androgen Antagonists
  • Androgens
  • Antineoplastic Agents, Hormonal
  • Flutamide
  • Cyproterone
  • Leuprolide