Meningiomas e o microambiente tumoral: a expressão da molécula moduladora imune PD-L1 e do Interferon-Gama no prognóstico

• Ano de defesa: 2019
• Autor(a) principal: Gerson, Gunter
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Meningioma; Microambiente Tumoral; Prognóstico; Interferon gama
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/45154

Meningiomas are the most common intracranial tumors in adults, accounting for approximately 35% of primary tumors of the central nervous system (CNS). One of the mechanisms used by tumor cells to escape death by immune cells is to interfere with immunological checkpoints, thereby preventing the establishment of adequate immune response. Following this concept, a promising target for an immunomodulatory therapy is programmed cell death block 1 (PD-1) / programmed cell death ligand 1 (PD-L1), which is known to be crucial for immune escape mechanisms. Interferon gamma (IFN-γ) is related to the expression of PD-L1, being produced by active T cells and may promote hyper-regulation of PD-L1 expression in tumor cells. The present work proposes to evaluate the expression of PD-L1 and IFN-γ and its relation with progression-free time and tumor recurrence in meningiomas, and to analyze the correlation between clinical and morphological aspects with the immunoexpression of these markers. The study was a cross-sectional retrospective cohort that analyzed 93 patients diagnosed with meningioma of varying degrees. Paraffin blocks containing samples from all tumors were made using the TMA - tissue micro array technique, and immunohistochemical reactions of PD - L1 and IFN - γ proteins were performed. The study confirmed that several clinical and morphological variables are related to a worse prognosis with higher rates of recurrence and reduction of progression-free time of the disease. This study did not detect PD-L1 immunoexpression in any of the 93 analyzed cases and showed that patients with IFN-γ immunoexpression had lower rates of tumor recurrence and longer disease progression free time, absence of pleomorphism, better differentiation and lower tumor grade. The expression of PDL1 in meningioma cells and their potential role in local immunosuppression is not fully established and their indication of anti-PD-L1 therapy as an alternative treatment for menin-giomas is still controversial. Patients with IFN-γ immunoexpression had lower rates of tumor recurrence, longer disease-free survival time. The IFN-γ immunoexpression was also related to the absence of pleomorphism in the tumor cells and lower tumor degree.