• Citer

Impact of treatments on the clinical value of immune response in breast cancer: an insilico analysis

par Jose, Vinu
Président du jury Maenhaut, Carine
Promoteur Sotiriou, Christos
Publication Non publié, 2023-09-25

Thèse de doctorat

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

Immune response to breast cancer (immunogenicity of breast cancer) has clinical relevance. Further, many studies report that traditional therapies affect immune response. For example, popular microtubule-targeting agents modulate immune cell function preclinically. This thesis investigates whether microtubule-targeting agents impact immune responses to breast cancer and their clinical relevance.Using the FinHER randomized phase III adjuvant trial comparing the microtubule-stabilizing agent Doxcetaxel to the microtubule-destabilizing agent Vinorelbine with FEC as backbone chemotherapy, the thesis explored the effect of microtubule-stabilizing and destabilizing agents on breast cancer immune response and patient survival. FinHER specimens were preserved as FFPE blocks. A pilot study was performed to determine whether gene modules derived from FFPE specimens profiled on Affymetrix arrays are reproducible. Additionally, FFPE expression profiles were analyzed for the reliability of published gene modules. The results of this study revealed 1) the loss of biological signals from FFPE expression profiles and 2) the feasibility of producing reproducible gene modules from FFPE specimens using Affymetrix arrays with FFPE-specific sample preparation protocols. Based on the pilot study results, FinHER FFPE specimens were profiled. Furthermore, published studies with chemotherapy regimen details were extracted from the GEO database and integrated for validation. The integration of published gene expression data from GEO was necessary since well-curated large public datasets like TCGA, METABRIC, and MetaGxBreast do not provide a detailed characterization of the chemotherapy regimen needed for validation. Using the FinHER and the integrated GEO datasets, the thesis demonstrated a potential interaction between microtubule targeting agents and immune response to clinical outcomes in adjuvant and neoadjuvant breast cancer settings. This interaction’s clinical relevance is discussed.In conclusion, the thesis demonstrates the potential impact of microtubule agents on the host immune response and its clinical relevance in breast cancer.