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Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses

Neutrophils are prominent immune components of tumors, having either anti-tumor (N1) or pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN are rare in non-pathol...

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Autores principales: Saraiva, Diana P., Correia, Bruna F., Salvador, Rute, de Sousa, Nídia, Jacinto, António, Braga, Sofia, Cabral, M. Guadalupe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629401/
https://www.ncbi.nlm.nih.gov/pubmed/34853660
http://dx.doi.org/10.18632/oncotarget.28135
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author Saraiva, Diana P.
Correia, Bruna F.
Salvador, Rute
de Sousa, Nídia
Jacinto, António
Braga, Sofia
Cabral, M. Guadalupe
author_facet Saraiva, Diana P.
Correia, Bruna F.
Salvador, Rute
de Sousa, Nídia
Jacinto, António
Braga, Sofia
Cabral, M. Guadalupe
author_sort Saraiva, Diana P.
collection PubMed
description Neutrophils are prominent immune components of tumors, having either anti-tumor (N1) or pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN are rare in non-pathological conditions, but frequent in cancer, exhibiting a pro-tumor phenotype. These findings have been mainly demonstrated in animal models, thus proper validation in humans is still imperative. Here, we observed that LDN were increased in the blood of breast cancer (BC) patients, particularly with metastatic disease. Within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than patients with a good response. The higher incidence of LDN in BC patients with severe disease or resistance to treatment can be explained by their pro-tumor/immunosuppressive characteristics. Moreover, the percentage of LDN in BC patients’ blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with immunosuppressive regulatory T cells. The ability of LDN to spoil anti-tumor immune responses was further demonstrated ex vivo. Hence, this study reveals the potential of LDN as a biomarker of BC response to treatment and opens new avenues for developing new immunotherapies.
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spelling pubmed-86294012021-11-30 Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses Saraiva, Diana P. Correia, Bruna F. Salvador, Rute de Sousa, Nídia Jacinto, António Braga, Sofia Cabral, M. Guadalupe Oncotarget Research Paper Neutrophils are prominent immune components of tumors, having either anti-tumor (N1) or pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN are rare in non-pathological conditions, but frequent in cancer, exhibiting a pro-tumor phenotype. These findings have been mainly demonstrated in animal models, thus proper validation in humans is still imperative. Here, we observed that LDN were increased in the blood of breast cancer (BC) patients, particularly with metastatic disease. Within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than patients with a good response. The higher incidence of LDN in BC patients with severe disease or resistance to treatment can be explained by their pro-tumor/immunosuppressive characteristics. Moreover, the percentage of LDN in BC patients’ blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with immunosuppressive regulatory T cells. The ability of LDN to spoil anti-tumor immune responses was further demonstrated ex vivo. Hence, this study reveals the potential of LDN as a biomarker of BC response to treatment and opens new avenues for developing new immunotherapies. Impact Journals LLC 2021-11-23 /pmc/articles/PMC8629401/ /pubmed/34853660 http://dx.doi.org/10.18632/oncotarget.28135 Text en Copyright: © 2021 Saraiva et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Saraiva, Diana P.
Correia, Bruna F.
Salvador, Rute
de Sousa, Nídia
Jacinto, António
Braga, Sofia
Cabral, M. Guadalupe
Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses
title Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses
title_full Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses
title_fullStr Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses
title_full_unstemmed Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses
title_short Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses
title_sort circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of t cell responses
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629401/
https://www.ncbi.nlm.nih.gov/pubmed/34853660
http://dx.doi.org/10.18632/oncotarget.28135
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