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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
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.
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.
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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