Mannose Receptor-positive Macrophage Infiltration Correlates with Prostate Cancer Onset and Metastatic Castration-resistant Disease.
Eur Urol Oncol
; 2(4): 429-436, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31277779
ABSTRACT
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, ANDPARTICIPANTS:
Normal prostate tissue, localized PC, and mCRPC samples from 192 patients were retrospectively analyzed. OUTCOME MEASUREMENTS AND STATISTICALANALYSIS:
We analytically validated an immunohistochemistry assay for detection of the human mannose receptor (CD206) to assess M2 macrophage involvement. RESULTS ANDLIMITATIONS:
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. PATIENTSUMMARY:
In this report we used 192 prostate cancer samples to determine if M2 macrophage infiltration is correlated with castration resistance in prostate cancer.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Superfície Celular
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Lectinas Tipo C
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Lectinas de Ligação a Manose
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Neoplasias de Próstata Resistentes à Castração
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Macrófagos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article