Mannose Receptor-positive Macrophage Infiltration Correlates with Prostate Cancer Onset and Metastatic Castration-resistant Disease.
Castration-resistant prostate cancer
M2 tumor-associated macrophages
Mannose receptor
Prostate cancer
Journal
European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
18
05
2018
revised:
28
08
2018
accepted:
26
09
2018
entrez:
7
7
2019
pubmed:
7
7
2019
medline:
30
5
2020
Statut:
ppublish
Résumé
M2 tumor-associated macrophages (M2-TAMs) can suppress inflammation in the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported M2-TAM infiltration in metastatic castration-resistant prostate cancer (mCRPC). To determine whether the extent of M2-TAM infiltration correlates with PC aggressiveness. Normal prostate tissue, localized PC, and mCRPC samples from 192 patients were retrospectively analyzed. We analytically validated an immunohistochemistry assay for detection of the human mannose receptor (CD206) to assess M2 macrophage involvement. Multiplex immunofluorescent staining showed that a small fraction of CD206 staining co-localized with the endothelial cells of lymphatic vessels, while the vast majority of staining occurred in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion from normal (ie, no inflammation) prostate tissue, to primary untreated carcinomas, to hormone-naïve regional lymph node metastases, to mCRPC. Complementary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Limitations include the small number of rapid autopsy samples and the lack of neuroendocrine PC samples. Our results revealed a progressive increase in CD206-positive macrophages from normal prostate to mCRPC. Given the immunosuppressive nature of macrophages and the lack of clinical success of immunotherapy for PC patients, our results provide a rationale for therapeutic targeting of macrophages in the PC microenvironment as a potential method to augment immunotherapeutic responses. In this report we used 192 prostate cancer samples to determine if M2 macrophage infiltration is correlated with castration resistance in prostate cancer.
Sections du résumé
BACKGROUND
M2 tumor-associated macrophages (M2-TAMs) can suppress inflammation in the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported M2-TAM infiltration in metastatic castration-resistant prostate cancer (mCRPC).
OBJECTIVE
To determine whether the extent of M2-TAM infiltration correlates with PC aggressiveness.
DESIGN, SETTING, AND PARTICIPANTS
Normal prostate tissue, localized PC, and mCRPC samples from 192 patients were retrospectively analyzed.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
We analytically validated an immunohistochemistry assay for detection of the human mannose receptor (CD206) to assess M2 macrophage involvement.
RESULTS AND LIMITATIONS
Multiplex immunofluorescent staining showed that a small fraction of CD206 staining co-localized with the endothelial cells of lymphatic vessels, while the vast majority of staining occurred in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion from normal (ie, no inflammation) prostate tissue, to primary untreated carcinomas, to hormone-naïve regional lymph node metastases, to mCRPC. Complementary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Limitations include the small number of rapid autopsy samples and the lack of neuroendocrine PC samples.
CONCLUSIONS
Our results revealed a progressive increase in CD206-positive macrophages from normal prostate to mCRPC. Given the immunosuppressive nature of macrophages and the lack of clinical success of immunotherapy for PC patients, our results provide a rationale for therapeutic targeting of macrophages in the PC microenvironment as a potential method to augment immunotherapeutic responses.
PATIENT SUMMARY
In this report we used 192 prostate cancer samples to determine if M2 macrophage infiltration is correlated with castration resistance in prostate cancer.
Identifiants
pubmed: 31277779
pii: S2588-9311(18)30174-3
doi: 10.1016/j.euo.2018.09.014
pmc: PMC7039332
mid: NIHMS1554363
pii:
doi:
Substances chimiques
Lectins, C-Type
0
Mannose Receptor
0
Mannose-Binding Lectins
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
429-436Subventions
Organisme : NCI NIH HHS
ID : P01 CA093900
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA058236
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA143055
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA163124
Pays : United States
Informations de copyright
Copyright © 2018. Published by Elsevier B.V.
Références
Oncogene. 2014 May 8;33(19):2423-31
pubmed: 23728338
Methods Mol Med. 2005;103:89-101
pubmed: 15542899
Cancer Res. 1995 Apr 1;55(7):1499-504
pubmed: 7533663
Immunol Today. 1992 Jul;13(7):265-70
pubmed: 1388654
N Engl J Med. 2012 Jun 28;366(26):2443-54
pubmed: 22658127
Scand J Immunol. 2008 May;67(5):453-63
pubmed: 18405323
Curr Opin Pharmacol. 2013 Aug;13(4):595-601
pubmed: 23773801
Oncoimmunology. 2014 Jul 03;3(7):e941734
pubmed: 25954596
Mol Cell Proteomics. 2017 Jun;16(6):1029-1037
pubmed: 28348171
Oncol Lett. 2016 May;11(5):3403-3408
pubmed: 27123124
Blood. 2004 Oct 15;104(8):2224-34
pubmed: 15231578
Am J Clin Pathol. 2017 Nov 2;148(5):398-415
pubmed: 29106457
Eur Urol. 2019 Jan;75(1):88-99
pubmed: 29673712
Neoplasia. 2007 Jul;9(7):556-62
pubmed: 17710158
Semin Oncol. 2014 Apr;41(2):267-80
pubmed: 24787298
Eur J Cancer. 2006 Apr;42(6):717-27
pubmed: 16520032
Neoplasia. 2009 Nov;11(11):1235-42
pubmed: 19881959
N Engl J Med. 2012 Jun 28;366(26):2455-65
pubmed: 22658128
PLoS One. 2013 Oct 04;8(10):e76773
pubmed: 24124593
Cancer Microenviron. 2013 Aug;6(2):179-91
pubmed: 23179263
Nat Med. 2017 May;23(5):551-555
pubmed: 28346412
Clin Cancer Res. 2017 Nov 15;23(22):6764-6770
pubmed: 28663235
Cancer Res. 2006 Jan 15;66(2):605-12
pubmed: 16423985
Trends Immunol. 2002 Nov;23(11):549-55
pubmed: 12401408
Clin Cancer Res. 2011 Oct 15;17(20):6563-73
pubmed: 21878536
Clin Exp Metastasis. 2012 Aug;29(6):585-601
pubmed: 22484917
Am J Cancer Res. 2013 Nov 01;3(5):523-9
pubmed: 24224130
BJU Int. 2011 Jun;107(12):1918-22
pubmed: 21044246
CA Cancer J Clin. 2017 Jan;67(1):7-30
pubmed: 28055103
Biotechniques. 2016 Jul 01;61(1):33-41
pubmed: 27401672