Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils

Abstract Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local...

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Autores principales:	Karla Lucia Fernandez Alvarez, Mariana Beldi, Fabiane Sarmanho, Renata Ariza Marques Rossetti, Caio Raony Farina Silveira, Giana Rabello Mota, Maria Antonieta Andreoli, Eliana Dias de Carvalho Caruso, Marcia Ferreira Kamillos, Ana Marta Souza, Haydee Mastrocalla, Maria Alejandra Clavijo-Salomon, José Alexandre Marzagão Barbuto, Noely Paula Lorenzi, Adhemar Longatto-Filho, Edmund Baracat, Rossana Verónica Mendoza Lopez, Luisa Lina Villa, Maricy Tacla, Ana Paula Lepique
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d9d6263aa184d768c0d46a69d067d8b
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spelling	oai:doaj.org-article:1d9d6263aa184d768c0d46a69d067d8b2021-12-02T15:05:07ZLocal and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils10.1038/s41598-017-09079-32045-2322https://doaj.org/article/1d9d6263aa184d768c0d46a69d067d8b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09079-3https://doaj.org/toc/2045-2322Abstract Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.Karla Lucia Fernandez AlvarezMariana BeldiFabiane SarmanhoRenata Ariza Marques RossettiCaio Raony Farina SilveiraGiana Rabello MotaMaria Antonieta AndreoliEliana Dias de Carvalho CarusoMarcia Ferreira KamillosAna Marta SouzaHaydee MastrocallaMaria Alejandra Clavijo-SalomonJosé Alexandre Marzagão BarbutoNoely Paula LorenziAdhemar Longatto-FilhoEdmund BaracatRossana Verónica Mendoza LopezLuisa Lina VillaMaricy TaclaAna Paula LepiqueNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karla Lucia Fernandez Alvarez Mariana Beldi Fabiane Sarmanho Renata Ariza Marques Rossetti Caio Raony Farina Silveira Giana Rabello Mota Maria Antonieta Andreoli Eliana Dias de Carvalho Caruso Marcia Ferreira Kamillos Ana Marta Souza Haydee Mastrocalla Maria Alejandra Clavijo-Salomon José Alexandre Marzagão Barbuto Noely Paula Lorenzi Adhemar Longatto-Filho Edmund Baracat Rossana Verónica Mendoza Lopez Luisa Lina Villa Maricy Tacla Ana Paula Lepique Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils
description	Abstract Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.
format	article
author	Karla Lucia Fernandez Alvarez Mariana Beldi Fabiane Sarmanho Renata Ariza Marques Rossetti Caio Raony Farina Silveira Giana Rabello Mota Maria Antonieta Andreoli Eliana Dias de Carvalho Caruso Marcia Ferreira Kamillos Ana Marta Souza Haydee Mastrocalla Maria Alejandra Clavijo-Salomon José Alexandre Marzagão Barbuto Noely Paula Lorenzi Adhemar Longatto-Filho Edmund Baracat Rossana Verónica Mendoza Lopez Luisa Lina Villa Maricy Tacla Ana Paula Lepique
author_facet	Karla Lucia Fernandez Alvarez Mariana Beldi Fabiane Sarmanho Renata Ariza Marques Rossetti Caio Raony Farina Silveira Giana Rabello Mota Maria Antonieta Andreoli Eliana Dias de Carvalho Caruso Marcia Ferreira Kamillos Ana Marta Souza Haydee Mastrocalla Maria Alejandra Clavijo-Salomon José Alexandre Marzagão Barbuto Noely Paula Lorenzi Adhemar Longatto-Filho Edmund Baracat Rossana Verónica Mendoza Lopez Luisa Lina Villa Maricy Tacla Ana Paula Lepique
author_sort	Karla Lucia Fernandez Alvarez
title	Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils
title_short	Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils
title_full	Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils
title_fullStr	Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils
title_full_unstemmed	Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils
title_sort	local and systemic immunomodulatory mechanisms triggered by human papillomavirus transformed cells: a potential role for g-csf and neutrophils
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1d9d6263aa184d768c0d46a69d067d8b
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Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils

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