Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/105853 https://doi.org/10.3390/cancers12040818 |
Resumo: | In colon cancer, the prognostic value of macrophages is controversial, and it is still unknown how hypoxia modulates macrophage-cancer cell crosstalk. To unravel this, co-cultures of human primary macrophages and colon cancer cells were performed at 20% and 1% O2, followed by characterization of both cellular components. Different colon cancer patient cohorts were analyzed for hypoxia and immune markers, and their association with patient overall survival was established. A positive correlation between HIF1A and CD68 in colon cancer patients was identified but, unexpectedly, in cases with higher macrophage infiltration, HIF1A expression was associated with a better prognosis, in contrast to breast, gastric, and lung cancers. Under hypoxia, co-cultures' secretome indicated a shift towards a pro-inflammatory phenotype. These alterations occurred along with increased macrophage phagocytic activity and decreased SIRPα expression. Cancer cells were more invasive and exhibited higher CD47 expression. We hypothesize that the better prognosis associated with HIF1AHighCD68High tumors could occur due to macrophagic pro-inflammatory pressure. Indeed, we found that tumors HIF1AHighCD68High expressed increased levels of CD8A, which is positively correlated with HIF1A. In conclusion, we show that in colon cancer, hypoxia drives macrophages into a pro-inflammatory phenotype, concomitant with increased infiltration of anti-tumor immune cells, favoring better disease outcome. |
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Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancerhypoxiamacrophagescolon cancertumor microenvironmentimmune cell infiltrationprognosisIn colon cancer, the prognostic value of macrophages is controversial, and it is still unknown how hypoxia modulates macrophage-cancer cell crosstalk. To unravel this, co-cultures of human primary macrophages and colon cancer cells were performed at 20% and 1% O2, followed by characterization of both cellular components. Different colon cancer patient cohorts were analyzed for hypoxia and immune markers, and their association with patient overall survival was established. A positive correlation between HIF1A and CD68 in colon cancer patients was identified but, unexpectedly, in cases with higher macrophage infiltration, HIF1A expression was associated with a better prognosis, in contrast to breast, gastric, and lung cancers. Under hypoxia, co-cultures' secretome indicated a shift towards a pro-inflammatory phenotype. These alterations occurred along with increased macrophage phagocytic activity and decreased SIRPα expression. Cancer cells were more invasive and exhibited higher CD47 expression. We hypothesize that the better prognosis associated with HIF1AHighCD68High tumors could occur due to macrophagic pro-inflammatory pressure. Indeed, we found that tumors HIF1AHighCD68High expressed increased levels of CD8A, which is positively correlated with HIF1A. In conclusion, we show that in colon cancer, hypoxia drives macrophages into a pro-inflammatory phenotype, concomitant with increased infiltration of anti-tumor immune cells, favoring better disease outcome.MDPI2020-03-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105853http://hdl.handle.net/10316/105853https://doi.org/10.3390/cancers12040818eng2072-6694Martins, FláviaOliveira, RosaCavadas, BrunoPinto, FilipeCardoso, Ana PatríciaCastro, FláviaSousa, BárbaraPinto, Marta LaranjeiroSilva, Ana JoãoAdão, DiogoLoureiro, José PedroPedro, NicoleReis, Rui ManuelPereira, LuísaOliveira, Maria JoséCosta, Angela Margaridainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-13T21:31:25ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer |
title |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer |
spellingShingle |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer Martins, Flávia hypoxia macrophages colon cancer tumor microenvironment immune cell infiltration prognosis |
title_short |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer |
title_full |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer |
title_fullStr |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer |
title_full_unstemmed |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer |
title_sort |
Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer |
author |
Martins, Flávia |
author_facet |
Martins, Flávia Oliveira, Rosa Cavadas, Bruno Pinto, Filipe Cardoso, Ana Patrícia Castro, Flávia Sousa, Bárbara Pinto, Marta Laranjeiro Silva, Ana João Adão, Diogo Loureiro, José Pedro Pedro, Nicole Reis, Rui Manuel Pereira, Luísa Oliveira, Maria José Costa, Angela Margarida |
author_role |
author |
author2 |
Oliveira, Rosa Cavadas, Bruno Pinto, Filipe Cardoso, Ana Patrícia Castro, Flávia Sousa, Bárbara Pinto, Marta Laranjeiro Silva, Ana João Adão, Diogo Loureiro, José Pedro Pedro, Nicole Reis, Rui Manuel Pereira, Luísa Oliveira, Maria José Costa, Angela Margarida |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Martins, Flávia Oliveira, Rosa Cavadas, Bruno Pinto, Filipe Cardoso, Ana Patrícia Castro, Flávia Sousa, Bárbara Pinto, Marta Laranjeiro Silva, Ana João Adão, Diogo Loureiro, José Pedro Pedro, Nicole Reis, Rui Manuel Pereira, Luísa Oliveira, Maria José Costa, Angela Margarida |
dc.subject.por.fl_str_mv |
hypoxia macrophages colon cancer tumor microenvironment immune cell infiltration prognosis |
topic |
hypoxia macrophages colon cancer tumor microenvironment immune cell infiltration prognosis |
description |
In colon cancer, the prognostic value of macrophages is controversial, and it is still unknown how hypoxia modulates macrophage-cancer cell crosstalk. To unravel this, co-cultures of human primary macrophages and colon cancer cells were performed at 20% and 1% O2, followed by characterization of both cellular components. Different colon cancer patient cohorts were analyzed for hypoxia and immune markers, and their association with patient overall survival was established. A positive correlation between HIF1A and CD68 in colon cancer patients was identified but, unexpectedly, in cases with higher macrophage infiltration, HIF1A expression was associated with a better prognosis, in contrast to breast, gastric, and lung cancers. Under hypoxia, co-cultures' secretome indicated a shift towards a pro-inflammatory phenotype. These alterations occurred along with increased macrophage phagocytic activity and decreased SIRPα expression. Cancer cells were more invasive and exhibited higher CD47 expression. We hypothesize that the better prognosis associated with HIF1AHighCD68High tumors could occur due to macrophagic pro-inflammatory pressure. Indeed, we found that tumors HIF1AHighCD68High expressed increased levels of CD8A, which is positively correlated with HIF1A. In conclusion, we show that in colon cancer, hypoxia drives macrophages into a pro-inflammatory phenotype, concomitant with increased infiltration of anti-tumor immune cells, favoring better disease outcome. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-03-28 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/105853 http://hdl.handle.net/10316/105853 https://doi.org/10.3390/cancers12040818 |
url |
http://hdl.handle.net/10316/105853 https://doi.org/10.3390/cancers12040818 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2072-6694 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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repository.mail.fl_str_mv |
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