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Pegylated-interferon-alpha treatment modifying T cell cytokine profile in tumor microenvironment of patients with cervical intraepithelial neoplasia

  • Fabiano Vilela Mundim1
  • Marco Aurélio Trovó2
  • Letícia Montes Stark3
  • Millena Prata Jammal4
  • Márcia Antoniazi Michelin1
  • Eddie Fernando Candido Murta4,*,

1Research Institute of Oncology (IPON)/Discipline of Immunology-Federal University of Triângulo Mineiro (UFTM), Uberaba, 38064200 MG, Brazil

2Department of Gynecology and Obstetrics-Federal University of Triângulo Mineiro (UFTM), Uberaba, 38.025-440 MG, Brazil

3Research Institute of Oncology (IPON)-Federal University of Triângulo Mineiro (UFTM), Uberaba, 38.025-440 MG, Brazil

4Research Institute of Oncology (IPON)/Department of Gynecology and Obstetrics-Federal University of Triângulo Mineiro (UFTM), Uberaba, 38064200 MG, Brazil

DOI: 10.31083/j.ejgo.2021.01.2265 Vol.42,Issue 1,February 2021 pp.96-104

Submitted: 06 October 2020 Accepted: 12 December 2020

Published: 15 February 2021

*Corresponding Author(s): Eddie Fernando Candido Murta E-mail:


Objective: The goal of the investigation was to compare the profiles the cytokines IL-2, IL-12, IFN-γ, TNF-α , TGF-β, IL-4, IL-6 in the endocervical and serum secretions of patients with cervical intraepithelial neoplasia (CIN) who had good or poor response to immunotherapy with pegylated (PEG)-Interferon-alpha. Methods: The study was performed with 16 patients who had been diagnosed with CIN II and III. Each patient was submitted to six injections of PEG-Interferon-α -2b subcutaneously. After each injection, endocervical secretion and serum samples were collected for cytokine levels by ELISA. Results: Of the 16 women, 43.75% (n = 7) showed good clinical response and lesion regression after treatment as seen by histopathological analysis. When we analyzed the pre-therapy, locally we observed a higher concentration of IL-4 in patients who did not respond to treatment (P = 0.0229). After treatment, there was a significant reduction in IL-4 in unresponsive patients (P = 0.0304). Patients responsive to IFN-α had a reduction in the concentrations the TNF-α after treatment (P = 0.0313). Conclusion: Immunotherapy with PEG-Interferon-α can reduce the damage caused by HPV by decreasing local inflammation by reducing the cytokines IL-4 and TNF-alpha during treatment in endocervical secretion. It seems that the regression is related to the immunological profile, mainly local, before treatment, as in the case of IL-4 and TNF-alpha, promoting a Th2 profile in those patients with therapeutic failure.


Cytokines; Immunotherapy; Cervical intraepithelial neoplasia

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Fabiano Vilela Mundim,Marco Aurélio Trovó,Letícia Montes Stark,Millena Prata Jammal,Márcia Antoniazi Michelin,Eddie Fernando Candido Murta. Pegylated-interferon-alpha treatment modifying T cell cytokine profile in tumor microenvironment of patients with cervical intraepithelial neoplasia. European Journal of Gynaecological Oncology. 2021. 42(1);96-104.


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