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Understanding tertiary lymphoid structure formation and function in anti-tumor immune responses to breast cancer

ABG-87819 Sujet de Thèse
09/10/2019 > 25 et < 35 K€ brut annuel
Université Libre de Bruxelles_Institut Jules Bordet
Bruxelles - Belgique
Understanding tertiary lymphoid structure formation and function in anti-tumor immune responses to breast cancer
  • Santé, médecine humaine, vétérinaire
  • Biologie
Tumor infiltrating lymphocytes, breast cancer, tertiary lymphoid structure

Description du sujet

The Molecular Immunology Unit (MIU) at the Institut Jules Bordet, Université Libre de Bruxelles focuses on both fundamental and translational research related to understanding normal lymphocyte functions and how they deviate in human disease. Our
prospective breast cancer (BC) study (current accrual >800 patients) found that global tumor infiltrating lymphocytes (TIL) form a continuum with approximately 75% of tumors identified as TIL-positive. TILpos tumors are equally divided into TILintermediate and TIL-high based on thresholds defined by control breast tissues (Buisseret et al. Oncoimmunology, 2016). Further, 60% of BC were found to have TIL organized in one or more tertiary lymphoid structures (TLS) principally located in the tumor stroma. The architecture of a TLS is similar to secondary lymphoid organs and mucosal associated lymphoid tissues such as tonsils with a T cell zone adjacent to a B cell follicle
containing a germinal center and specialized CD4+ T cells called T follicular helper cells (Tfh) (Garaud et al., JCI Insight, 2019). Our previous studies also show that TfhX13 TIL (CXCR5–PD-1hiICOSintCD4+) produce the B cell chemoattractant CXCL13 (Gu-Trantien et al., JCI Insight, 2017).

TLS may provide a site for T- and B-TIL cooperation near the tumor bed, thereby fostering the generation of antigen-specific immune responses in a protected environment and favoring the production of anti-tumor memory cells that help control residual
disease. However, the balance and function of TIL subpopulations in BC-associated TLS is currently not well understood.

In the particular project for which the PhD student is hired, she/he will investigate the balance and function of TIL subpopulations in BC-associated TLS. In this work, the PhD student will use approaches of flow cytometry, molecular biology, cellular biology and tissue imaging to investigate TLS.

Prise de fonction :

01/11/2019

Nature du financement

Contrat doctoral

Précisions sur le financement

Présentation établissement et labo d'accueil

Université Libre de Bruxelles_Institut Jules Bordet

The Institut Jules Bordet is an integrated, multidisciplinary centre, unique in Belgium and which enjoys an international reputation. The hospital is devoted entirely to patients affected by cancer. For more than 75 years, our teams have been offering patients leading-edge diagnostic and therapeutic strategies in the prevention, screening and active treatment of all types of cancer. The Institut Bordet also carries out important research activities which every year lead to major discoveries, as well as providing high-level, specialised university training.

The Molecular Immunology Unit strives to improve our understanding of the immune response in cancer and how it can be manipulated to the benefit of the patients. It investigates lymphocyte activities in several clinical conditions:   First, by studying the organization and cellular state of CD4+ T cells and germinal center B cells infiltrating the breast cancer microenvironment. This work involves both prospective studies designed to understand the functionality and subpopulations of tumor infiltrating lymphocytes present as well as their organization in peritumoral tertiary lymphoid structures, and retrospective studies that seek to apply these findings in the establishment of an immunological grade for breast cancer. Second, by identifying and characterizing specific changes in gene expression associated with clinical progression during the transition from pre-malignant disease to full-blown malignancy in patients with hypereosinophilic syndrome that develop T cell leukemia/lymphoma. Third, by analyzing specific changes in lymphocyte gene expression, with a focus on transcription factors regulating their normal activities, which are aberrantly regulated in human cancer. Our ultimate goal in the fight against cancer is to further understand how we can harness the power and the specificity of the immune response through its revitalization in the hostile tumor microenvironment to produce effective and sustained anti-tumor immunity.

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Intitulé du doctorat

Doctorat en Sciences Biomédicales et Pharmaceutiques

Pays d'obtention du doctorat

Belgique

Etablissement délivrant le doctorat

Université Libre de Bruxelles

Ecole doctorale

Faculté de Médecine

Profil du candidat

We are looking for a talented and motivated doctoral student. Applicants should hold a Master or equivalent academic degree that is acceptable for admission as a PhD student at the Faculty of  Medicine of the Université Libre de Bruxelles. Experience in immunology, flow cytometry, molecular biology, cell biology and tissue imaging is welcome and will be an advantage.

Date limite de candidature

31/10/2019
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