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

• Autor(a) principal: Alvarez, Karla Lucia Fernandez
• Data de Publicação: 2017
• Outros Autores: Beldi, Mariana Carmezim, Sarmanho, Fabiane, Rossetti, Renata Ariza Marques, Silveira, Caio Raony Farina, Mota, Giana Rabello, Andreoli, Maria Antonieta, Caruso, Eliana Dias de Carvalho, Kamillos, Marcia Ferreira, Souza, Ana Marta, Mastrocalla, Haydee, Clavijo-Salomon, Maria Alejandra, Barbuto, José Alexandre Marzagão, Lorenzi, Noely Paula, Longatto Filho, Adhemar, Baracat, Edmund Chada, Lopez, Rossana Verónica Mendoza, Villa, Luisa Lina, Tacla, Maricy, Lepique, Ana Paula
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/48470
• topic: Science & Technology

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.