Pegylated-interferon-alpha treatment modulating the immune response of cytotoxic lymphocytes in cervical intraepithelial neoplasia

Abstract

Pegylated-interferon-alpha treatment modulating the immune response of cytotoxic lymphocytes in cervical intraepithelial neoplasia Letícia Montes Stark1 , Rosekeila Simões Nomelini1,2 , Marco Aurélio Trovó2 , Márcia Antoniazi Michelin1,3 , Eddie Fernando Candido Murta1,2, * 1Oncology Research Institute (IPON), Federal University of the Triângulo Mineiro (UFTM), 38025-440 Uberaba, Minas Gerais, Brazil 2Department of Gynecology and Obstetrics, Federal University of the Triângulo Mineiro (UFTM), 38071-200 Uberaba, Minas Gerais, Brazil 3Discipline of Immunology, Federal University of the Triângulo Mineiro (UFTM), 38071-200 Uberaba, Minas Gerais, Brazil *Correspondence: eddiemurta@mednet.com.br (Eddie Fernando Candido Murta) DOI:10.31083/j.ceog.2021.03.2347 This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/). Submitted: 4 November 2020 Revised: 15 February 2021 Accepted: 5 March 2021 Published: 15 June 2021 Background: Interferons are inducible secretory glycoproteins with immunomodulators, antiviral, antiangiogenic and antiproliferative eȞfects. Evaluate the mechanisms responsible by regression of patients diagnosed with Cervical Intraepithelial Neoplasia (CIN) and treated with IFN-α, systemically and locally, by Interferon-α (IFNα) receptor 1 (IFNR1) and IFN-α receptor 2 (IFNR2) and transcription factors STAT-1 (Signal Transducers and Activators of Transcription 1) and IRF-7 (Interferon Regulatory Factor 7), as well as the endogenous produced IFN-α by total (CD3+), Helper (CD4+), cytotoxic (CD8+) T lymphocytes and monocytes (CD14+). Methods: A prospective study was developed in which eighteen patients diagnosed with CIN II/III in treatment protocol with Peginterferon-α. Cells were evaluated using Real-Time and Ƞlow cytometry, and the data were analyzed using Kruskal-Wallis and ANOVA tests, considering p ≤ 0.05. Results: Eight patients obtained regression of the lesion, and ten did not obtain the regression. Patients who did respond positively to the treatment presented a CD8+ T lymphocyte with IFN-α increase when compared to patients who not responded positively. When analyzing CD8+ T lymphocytes during the stages of treatment in lesion regression, it is observed a significant IFNR1 (p = 0.0391) decrease in patients who did not achieve lesion regression. CD3 and CD14 data was not significant. Discussion: Immunomodulation by Interferon-alpha seems to depend on the systemic expression of IFN receptors. Our data suggest that patients who can respond to immunotherapy already have a pattern of IFN receptor expression in lymphocytes, which contributes to successful treatment. Keywords Immunotherapy; Interferon-α; Cervical intraepithelial neoplasia