Browsing by Author "Teixeira, Pedro Noronha de Castro Machado"
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- Construction of a decision support system for the effectiveness of immune cell therapiesPublication . Teixeira, Pedro Noronha de Castro MachadoAbstract The ability to integrate immune responses from tumour infiltrating lymphocytes, TILs, whole blood assays (WBA) from flow cytometry data with the secretome through cytokine quantification using ELISA, makes it possible to optimise immune cell therapies. A centralised repository allows clinicians and researchers to unravel the complexities of immune responses triggered by various treatments in different patient groups. It promotes understanding of how immune cell therapies orchestrate their therapeutical effect. The aggregation of immunoreaction profiles paves the way for the identification of biomarkers that can anticipate the success of immune therapy interventions. In an era of personalised medicine, where healthcare providers can tailor immunotherapies according to the patient’s unique immunological landscape, therefore an organised storage of this data is required. In addition, longitudinal monitoring of immune responses provides information on the durability and evolution of therapeutic efficacy, revealing potential resistance mechanisms that may develop over time. As a proof of concept, two main assays using peripheral blood and tumourinfiltrating lymphocytes from patients with solid tumours, have been developed and optimised. Firstly, by placing immune cells from these two sources with synthetic peptides that are the same as the peptide sequences expressed in the solid tumor or patient-specific tumors, we can reveal functionality through the production of interferon gamma, IFN obtained through an ELISA assay and through the staining of intracellular cytokine staining carried out using flow cytometry. Secondly, evaluate the immune phenotype of TILs pre and post expansion and cytokine modulation and PBMCs phenotype to observe any changes. Subsequently, we performed statistical comparison tests to find any correlation between the phenotype of the immune cells and the detection of synthetic peptides via positive interferon-gamma production to reveal the potential effector functionality of the immune cells. Essentially, the integration of TIL, WBA data with ELISA and flow cytometry techniques in a decision support system not only speeds up the refinement of immune cells that have potential, but also constitutes a promising advance in the treatment of patients, because it leverages the advancement of personalised medicine. The aim of this study is to help develop accurate and effective analyses of ELISA and flow cytometry assays with the potential to reveal treatment options, which offers renewed hope for patients battling cancer and other immunemediated diseases. This study found a relationship between the Survivin mix (1-33), Survivin (97-111) and Mesothelin MPF-11 and the selected T cells, which suggests a degree of correlation. Thus, there is a potential functionality of the T cells selected from these epithelial tumour patient samples in response to a list of 30 test peptides.