Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs

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...

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Autores principales:	Clovis Boibessot, France-Hélène Joncas, Aerin Park, Zohra Berrehail, Jean-François Pelletier, Typhaine Gris, Alain Bergeron, Paul Toren
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ebf94ddf5f74989a2bbcafee09bf024
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spelling	oai:doaj.org-article:5ebf94ddf5f74989a2bbcafee09bf0242021-12-02T18:51:28ZUsing ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs10.1038/s41598-021-98903-y2045-2322https://doaj.org/article/5ebf94ddf5f74989a2bbcafee09bf0242021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98903-yhttps://doaj.org/toc/2045-2322Abstract 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.Clovis BoibessotFrance-Hélène JoncasAerin ParkZohra BerrehailJean-François PelletierTyphaine GrisAlain BergeronPaul TorenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Clovis Boibessot France-Hélène Joncas Aerin Park Zohra Berrehail Jean-François Pelletier Typhaine Gris Alain Bergeron Paul Toren Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs
description	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.
format	article
author	Clovis Boibessot France-Hélène Joncas Aerin Park Zohra Berrehail Jean-François Pelletier Typhaine Gris Alain Bergeron Paul Toren
author_facet	Clovis Boibessot France-Hélène Joncas Aerin Park Zohra Berrehail Jean-François Pelletier Typhaine Gris Alain Bergeron Paul Toren
author_sort	Clovis Boibessot
title	Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs
title_short	Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs
title_full	Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs
title_fullStr	Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs
title_full_unstemmed	Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs
title_sort	using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5ebf94ddf5f74989a2bbcafee09bf024
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Using ex vivo culture to assess dynamic phenotype changes in human prostate macrophages following exposure to therapeutic drugs

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