Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor-associated macrophage phenotype.
Clin Transl Med
; 12(1): e581, 2022 01.
Article
en En
| MEDLINE
| ID: mdl-35075795
ABSTRACT
Tumor-associated macrophages (TAMs) support tumor progression within the tumor microenvironment (TME). Many questions remain as to the origin, development, and function of TAMs within the prostate TME. Evaluation of TAMs in prostate cancer (PCa) patients identified the immunosuppressive TAM marker CD163 in adjacent normal epithelium as an independent predictor of metastases or PCa death. Flow cytometry analyses identified prostate TAMs as frequently expressing both proinflammatory M1 (CCR7+) and immunosuppressive M2 (CD163+) markers. In vitro, we demonstrate PCa cells similarly subvert human M1 macrophages toward a mixed M1/M2 macrophage phenotype favoring tumor growth. Further the cytokine milieu-induced transition between immunosuppressive M2 to proinflammatory M1 (M2âM1) macrophages is abrogated by the presence of PCa cells. RNA sequencing suggests alterations in chemokine expression in prostate TAMs due to the presence of PCa cells. Together, our results suggest that prostate TAMs originate from inflammatory infiltrating macrophages, which are then reprogrammed mainly by PCa cells, but also the cytokine milieu. A better understanding of this subversion of macrophages within the prostate may lead to novel treatment strategies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Próstata
/
Huésped Inmunocomprometido
/
Macrófagos
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Aged
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Clin Transl Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá