Avaliação das vias de sinalização do Interferon-alpha e do perfil de linfócitos T em pacientes com neoplasia intraepitelial cervical tratadas com Interferon-α 2b peguilado

Abstract

Interferons are inducible secretory glycoproteins with immunomodulators, antiviral, antiangiogenic and antiproliferative effects. Its antitumor effect has been researched under several pathological conditions, and it has been observed the development of escape mechanisms by the antitumor immune response, such as the downregulation of Interferonstimulated genes. The following research seeks to clarify the systemic responsiveness to Peginterferon Alfa-2B in patients diagnosed with Cervical Intraepithelial Neoplasia grades II and III, as well as the T lymphocytes cervical profile after treatment, in the interest of understanding the immunological mechanisms involved in lesion regression after immunotherapy. Objective: This study aims to evaluate, systemically and locally, Interferon-α receptors and transcription factors of T-bet, RORγT, STAT1 e IRF7, as well as the endogenous produced IFN-α by CD3+, CD4+, CD8+ T lymphocytes and monocytes (CD14+) in the peripheral blood of patients diagnosed with Cervical Intraepithelial Neoplasia, during treatment with Peginterferon Alfa-2B. Methods: A prospective study was developed in which eighteen patients diagnosed with CIN II and CIN III were included in treatment protocol with Peginterferon Alfa (subcutaneous injections with 80 μg / 0.5 mL per week, during six weeks). Cells were evaluated using Real-Time flow cytometry and the data was analyzed using Kruskal-Wallis, Wilcoxon 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 not respond positively to the treatment presented a CD4+ T lymphocyte with IFNR1 and IFNR2 (p = 0.0336; p = 0.0165) increase when compared to patients who responded positively. When analyzing CD8+ T lymphocytes during the stages of treatment in lesion regression, it is observed a significant IFNR1 (p=0.0391) and IRF7 (p=0.05) decrease in patients who did not achieve lesion regression when comparing the third and sixth applications. It was noticed an increase of RORγT local expression in patients who did not responded positively to the treatment compared to those who responded positively (p = 0.01). Conclusion: Analysis shows that treatment with Peginterferon Alfa significantly increased the RORγT local expression in patients who did not achieve lesion regression. These patients also presented an increase of CD4+ T lymphocytes IFNR1 and IFNR2. This data suggests that there may exist tumor escape mechanisms that avoid lesion elimination by Peginterferon Alfa immunomodulation.