Year-end Sale % OFF 
Abstract
PurposeWe previously showed that autologous dendritic cells (DCs) loaded with an allogeneic heat shock (HS)-conditioned melanoma cell-derived lysate, called TRIMEL, induce T-cell-mediated immune responses in stage IV melanoma patients. Importantly, a positive delayed-type hypersensitivity (DTH) reaction against TRIMEL after vaccination, correlated with patients prolonged survival. Furthermore, we observed that DTH reaction was associated with a differential response pattern reflected in the presence of distinct cell subpopulations in peripheral blood. Detected variations in patient responses encouraged molecular studies aimed to identify gene expression profiles induced after vaccination in treated patients, allowing the identification of new molecular predictive markers.MethodsGene expression patterns were analyzed by microarrays during vaccination, and some of them confirmed by quantitative real-time reverse transcriptase PCR (qRT-PCR) in the total leukocyte population of a representative group of responder and non-responder patients. New candidates for biomarkers with predictive value were identified using bioinformatics, molecular analysis, and flow cytometry.ResultsSeventeen genes overexpressed in responder patients after vaccination respect to non-responders were identified after a mathematical analysis, from which ten were linked to immune responses and five related to cell cycle control and signal transduction. In immunological responder patients, increased protein levels of the chemokine receptor CXCR4 and the Fc-receptor CD32 were observed on cell membranes of CD8+ T and B cells and the monocyte population, respectively, confirming gene expression results.ConclusionsOur study contributes to finding new molecular markers associated with clinical outcome and better understanding of clinically relevant immunological responses induced by anti-tumor DC-vaccines.
Highlights
Influence of genetic predisposition in medical conditions is a relevant aspect to be evaluated related to the benefit of a specific drug or therapeutic approach
Seventeen genes overexpressed in responder patients after vaccination respect to non-responders were identified after a mathematical analysis, from which ten were linked to immune responses and five related to cell cycle control and signal transduction
Our study contributes to finding new molecular markers associated with clinical outcome and better understanding of clinically relevant immunological responses induced by anti-tumor dendritic cell (DC)-vaccines
Summary
Influence of genetic predisposition in medical conditions is a relevant aspect to be evaluated related to the benefit of a specific drug or therapeutic approach. The accumulated knowledge regarding immunological mechanisms involved in cancer dynamics has paved the way for novel therapeutic approaches that manipulate a patient’s immune system to control the disease [5]. These approaches include the use of: proinflammatory cytokines; fully humanized monoclonal antibodies (mAbs) directed against check-point molecules such as anti-CTLA4 and anti-PD-1/PD-L1 [6]; cell-based immunotherapies, such as adoptive transfer of CD8+ T lymphocytes [7, 8]; and several cancer vaccines, including autologous dendritic cell (DC)-based vaccines [9, 10]. Individual factors involved in the differential capacity of patients to respond to immunizations remain poorly understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
