Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotype
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctm2.581 |
| _version_ | 1798025347765108736 |
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| author | Clovis Boibessot Oscar Molina Gabriel Lachance Christophe Tav Audrey Champagne Bertrand Neveu Jean‐François Pelletier Frédéric Pouliot Vincent Fradet Steve Bilodeau Yves Fradet Alain Bergeron Paul Toren |
| author_facet | Clovis Boibessot Oscar Molina Gabriel Lachance Christophe Tav Audrey Champagne Bertrand Neveu Jean‐François Pelletier Frédéric Pouliot Vincent Fradet Steve Bilodeau Yves Fradet Alain Bergeron Paul Toren |
| author_sort | Clovis Boibessot |
| collection | DOAJ |
| description | 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 (M2→M1) 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. |
| first_indexed | 2024-04-11T18:17:25Z |
| format | Article |
| id | doaj.art-37123b3fa5984df0993a810535e42174 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-04-11T18:17:25Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-37123b3fa5984df0993a810535e421742022-12-22T04:09:51ZengWileyClinical and Translational Medicine2001-13262022-01-01121n/an/a10.1002/ctm2.581Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotypeClovis Boibessot0Oscar Molina1Gabriel Lachance2Christophe Tav3Audrey Champagne4Bertrand Neveu5Jean‐François Pelletier6Frédéric Pouliot7Vincent Fradet8Steve Bilodeau9Yves Fradet10Alain Bergeron11Paul Toren12Centre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaCentre de recherche du CHU de Québec—Université Laval Axe Oncologie Québec CanadaAbstract 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 (M2→M1) 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.https://doi.org/10.1002/ctm2.581CD163immunosuppressionmacrophagesphenotypeprostate cancer |
| spellingShingle | Clovis Boibessot Oscar Molina Gabriel Lachance Christophe Tav Audrey Champagne Bertrand Neveu Jean‐François Pelletier Frédéric Pouliot Vincent Fradet Steve Bilodeau Yves Fradet Alain Bergeron Paul Toren Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotype Clinical and Translational Medicine CD163 immunosuppression macrophages phenotype prostate cancer |
| title | Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotype |
| title_full | Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotype |
| title_fullStr | Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotype |
| title_full_unstemmed | Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotype |
| title_short | Subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor‐associated macrophage phenotype |
| title_sort | subversion of infiltrating prostate macrophages to a mixed immunosuppressive tumor associated macrophage phenotype |
| topic | CD163 immunosuppression macrophages phenotype prostate cancer |
| url | https://doi.org/10.1002/ctm2.581 |
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