Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role

Karla Lucia Fernandez Alvarez1, Mariana Beldi2, Fabiane Sarmanho2

  • 1Department of Immunology, Institute of Biomedical Sciences, Universidade de São Paulo, Av. Prof. Lineu Prestes, 1730, Ed. Biomédicas IV, 05508-900, São Paulo, SP, Brazil.

Scientific Reports
|August 23, 2017
PubMed

Insights

Human Papillomavirus (HPV) infection can lead to cervical cancer through immune evasion. This study found neutrophils and G-CSF promote immune escape locally and systemically in cervical cancer progression.

Area of Science:

  • Immunology
  • Oncology
  • Virology

Background:

  • Cervical cancer development involves Human Papillomavirus (HPV) infection and immune system interactions.
  • Immune evasion and tolerance to tumor antigens are key in cancer progression.
  • Understanding local and systemic immune changes is crucial for cervical cancer research.

Purpose of the Study:

  • To investigate local and systemic immune system alterations during cervical lesion progression to cancer.
  • To identify the roles of neutrophils, T cells, macrophages, and dendritic cells in cervical cancer immunity.
  • To explore the impact of G-CSF on immune cell function in cervical cancer.

Main Methods:

  • Analysis of leukocyte infiltrate in cervical tissues.
  • In vitro 3D tumor cell cultures to assess neutrophil-T cell interactions.
  • Quantification of plasma G-CSF concentrations and immune cell frequencies.
  • Correlation analysis between immune cell populations and plasma factors.

Main Results:

  • Increased T lymphocytes, neutrophils, and M2 macrophages in cervical cancer tissues.
  • Neutrophils inhibited T cell activity in vitro and showed increased viability and CD16 expression.
  • Higher plasma G-CSF, immature neutrophils, and tolerogenic MoDCs in cancer patients.
  • Negative correlation between T cell activation by MoDCs and plasma G-CSF.

Conclusions:

  • Neutrophils contribute to local immune suppression in cervical cancer.
  • Elevated G-CSF and immature neutrophils suggest systemic immune evasion mechanisms.
  • These findings highlight neutrophils and G-CSF as potential targets for cervical cancer immunotherapy.

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