Immune Biomarkers In Peripheral Blood In Patients With HER2 Negative Advanced Breast Cancer Treated With A Chemoimmunotherapy Schedule Based On Pembrolizumab And Gemcitabine. – Translational Substudy Of The PANGEA- Breast Cancer Trial (GEICAM/2015-04)

• Autores: Isabel Araujo Fernández
• Directores de la Tesis: Luis de la Cruz-Merino (dir. tes.), Víctor Sánchez-Margalet (dir. tes.)
• Lectura: En la Universidad de Sevilla ( España ) en 2022
• Idioma: inglés
• Número de páginas: 228
• Enlaces
  • Tesis en acceso abierto en: Idus
• Resumen

  • Within the last years, immune checkpoint inhibitors (ICI) have constituted a major breakthrough in cancer research. These molecules are monoclonal antibodies (mAb) with immunomodulatory properties as they target specific immune checkpoints located in both immune and cancer cells. These immunomodulatory antibodies have obtained indications in several settings of different tumour types as melanoma, classical Hodgkin lymphoma, non-small cell lung cancer (NSCLC), bladder cancer, head & neck cancer or renal cell carcinoma (RCC), among others. Although these drugs have demonstrated a positive impact on survival in randomized controlled trials (RCTs),their efficacy may vary across tumour types and different clinical settings, providing a relatively low proportion of responders in many cases. Therefore, the research of immune biomarkers is considered a need in order to select the subgroups of patients that benefit most from these drugs. In this context, the composition of the tumour microenvironment (TME) and immune profiling in peripheral blood are gaining great interest in relation to their potential impact in clinical practice. Some key elements, as myeloid derived suppressor cells (MDSC), regulatory T cells (Treg), programmed death ligand 1(PD-L1) expression or tumour infiltrating lymphocytes (TILs) density, may represent “bona-fide” markers of immune suppression or activation that could potentially predict responses to these drugs. Increasing translational data supports that the immunoediting process is also a hallmark of breast cancer and thus it was reasonable to explore the activity of these drugs, such as pembrolizumab, and even more, their potential synergism with some chemotherapy agents with well known immunogenic effects, such as gemcitabine. Within the PANGEA-Breast Cancer trial (GEICAM/2015-04), an ambitious plan of translational substudies in order to identify reliable immune biomarkers predicting clinical response was settled-up. In this thesis, we pursue to complete a comprehensive analysis of immune biomarkers like MDSCs, CD4 T cells, CD8 T cells and Treg cells counts in peripheral blood of the patients included in the PANGEA-trial in order to explore correlation with clinical outcomes.