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Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs.
Boibessot, Clovis; Joncas, France-Hélène; Park, Aerin; Berrehail, Zohra; Pelletier, Jean-François; Gris, Typhaine; Bergeron, Alain; Toren, Paul.
Afiliação
  • Boibessot C; Laboratoire d'Uro-Oncologie Expérimentale, Centre de recherche du CHU de Québec-Université Laval, Axe Oncologie, 10 McMahon, rm 0877, Quebec, QC, G1R 3S1, Canada.
  • Joncas FH; Centre de recherche sur le Cancer de l'Université Laval, Quebec, Canada.
  • Park A; Laboratoire d'Uro-Oncologie Expérimentale, Centre de recherche du CHU de Québec-Université Laval, Axe Oncologie, 10 McMahon, rm 0877, Quebec, QC, G1R 3S1, Canada.
  • Berrehail Z; Centre de recherche sur le Cancer de l'Université Laval, Quebec, Canada.
  • Pelletier JF; Laboratoire d'Uro-Oncologie Expérimentale, Centre de recherche du CHU de Québec-Université Laval, Axe Oncologie, 10 McMahon, rm 0877, Quebec, QC, G1R 3S1, Canada.
  • Gris T; Centre de recherche sur le Cancer de l'Université Laval, Quebec, Canada.
  • Bergeron A; Laboratoire d'Uro-Oncologie Expérimentale, Centre de recherche du CHU de Québec-Université Laval, Axe Oncologie, 10 McMahon, rm 0877, Quebec, QC, G1R 3S1, Canada.
  • Toren P; Centre de recherche sur le Cancer de l'Université Laval, Quebec, Canada.
Sci Rep ; 11(1): 19299, 2021 09 29.
Article em En | MEDLINE | ID: mdl-34588590
ABSTRACT
Within the prostate tumor microenvironment (TME) there are complex multi-faceted and dynamic communication occurring between cancer cells and immune cells. Macrophages are key cells which infiltrate and surround tumor cells and are recognized to significantly contribute to tumor resistance and metastases. Our understanding of their function in the TME is commonly based on in vitro and in vivo models, with limited research to confirm these model observations in human prostates. Macrophage infiltration was evaluated within the TME of human prostates after 72 h culture of fresh biopsies samples in the presence of control or enzalutamide. In addition to immunohistochemistry, an optimized protocol for multi-parametric evaluation of cellular surface markers was developed using flow cytometry. Flow cytometry parameters were compared to clinicopathological features. Immunohistochemistry staining for 19 patients with paired samples suggested enzalutamide increased the expression of CD163 relative to CD68 staining. Techniques to validate these results using flow cytometry of dissociated biopsies after 72 h of culture are described. In a second cohort of patients with Gleason grade group ≥ 3 prostate cancer, global macrophage expression of CD163 was unchanged with enzalutamide treatment. However, exploratory analyses of our results using multi-parametric flow cytometry for multiple immunosuppressive macrophage markers suggest subgroup changes as well as novel associations between circulating biomarkers like the neutrophil to lymphocyte ratio (NLR) and immune cell phenotype composition in the prostate TME. Further, we observed an association between B7-H3 expressing tumor-associated macrophages and the presence of intraductal carcinoma. The use of flow cytometry to evaluate ex vivo cultured prostate biopsies fills an important gap in our ability to understand the immune cell composition of the prostate TME. Our results highlight novel associations for further investigation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Feniltioidantoína / Neoplasias da Próstata / Benzamidas / Biomarcadores Tumorais / Macrófagos Associados a Tumor / Antagonistas de Androgênios / Nitrilas Tipo de estudo: Guideline / Observational_studies Limite: Aged / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Feniltioidantoína / Neoplasias da Próstata / Benzamidas / Biomarcadores Tumorais / Macrófagos Associados a Tumor / Antagonistas de Androgênios / Nitrilas Tipo de estudo: Guideline / Observational_studies Limite: Aged / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá