Circulatory biomarkers of melanoma metastasis

• Autor(a) principal: Maximino, José António Cordeiro Torres
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/158611
• topic: CM; biomarkers; CCR4 expression in Tregs; M1 and M2-like monocytes; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Cutaneous melanoma (CM) is the most aggressive and lethal type of skin cancer. Although the utilization of checkpoint inhibitor immunotherapies revolutionized the treatment of patients with melanoma, the number of responders is limited, and the survival of advanced stages still reduced. Considering that CM is one of the most immunogenic types of cancer, the immune system seems to be determinant in disease evolution and therapy response. This project intends to study the profile of immune cell populations in patients with CM, correlating with their clinical evolution, as to identify new promising biomarkers with prognostic and / or predictive value. The characterization of these populations was performed via flow cytometry in peripheral blood samples and surgical fragments from patients with CM stages II-IV followed at IPOLFG. Gene expression of immune response related genes was also evaluated, by Reverse Transcriptase Quantitative Polymerase Chain Reaction (RT-qPCR) in the fragments. In addition, attempts were made to establish primary cultures with the remaining material. It was possible to observe trends for a more immunosuppressive systemic environment in stage IV CM patients, characterized by the tendencies for the decrease of cluster of differentiation (CD)8+ T cells, their activation, and increase of regulatory T cells (Tregs). C-C motif chemokine receptor (CCR)4 expression in circulating Tregs tended to be reflected on the immune infiltrates, and higher expression levels may be associated with worse prognosis. Circulating M1 / M2-like monocyte populations were also identified, existing in higher quantity in CM patients when comparing to healthy controls, and tending to increase with disease severity. The predictive value of the immune populations was not possible to determine due to the very reduced number of samples. Viable CM primary cultures were not achieved, but experience and insight were gained for future attempts. Overall, the systemic immune profile of advanced CM patients starts to show promise as a potential prognostic tool, highlighting polarized monocytes as subpopulations of interest and CCR4 expression in Tregs.