Description du projet
Le microenvironnement tumoral fournit des indices pour une réponse d’immunothérapie
Les anticorps qui ciblent différents points de contrôle de la régulation immunitaire négative et rétablissent les réponses immunitaires anti-tumorales offrent des résultats cliniques prometteurs pour les patients atteints de mélanome. On comprend cependant encore mal pourquoi le pourcentage de patients à profiter d’une prolongation de la durée de vie, voire d’une rémission complète, reste si faible. Le projet cellsIMPACT, financé par l’UE, vise à découvrir de nouveaux biomarqueurs robustes pour prédire la réponse au traitement par inhibiteur de point de contrôle immunitaire (ICB, pour immune checkpoint blockade). Les chercheurs analyseront les biopsies tumorales et les échantillons de sang de patients atteints de mélanome et établiront des cartes dynamiques du microenvironnement tumoral après un traitement par ICB. L’intégration de ces informations aux données cliniques permettra d’identifier des facteurs déterminants du succès de l’immunothérapie.
Objectif
The fashion for tanned skin (in western countries) goes hand in hand with a high risk of getting melanoma: the most dangerous skin cancer. The recent development of novel classes of immunotherapies such as immune checkpoint blockade (ICB) for oncology has brought up hopes for the treatment of advanced-stage melanoma patients. Targeting immune checkpoints has reached remarkable clinical benefit in multiple cancers (especially in melanoma), enabling life extension and even complete remission in some cases. However, one of the current major limitations of ICB is that they cause durable clinical responses only in a relatively small number of patients and the reason behind this is still poorly understood. The central goal of this project is to discover novel and robust biomarkers predicting response to ICB as well as to understand the molecular mechanisms underlying therapy resistance (either intrinsic or acquired). I propose to establish dynamic maps of the evolving tumor ecosystem, including the tumor microenvironment (TME) landscape, at single-cell resolution during adaptive response to ICB. Pre- and on-treatment biopsies and blood samples from stage IV melanoma patients are currently being serially collected. I will analyze single cell RNA/DNA sequencing data obtained from these samples and integrate them with staining data from multiplex immunohistochemistry of the melanoma tissue. I will apply novel bioinformatic and statistical approaches to reach the ultimate aim: integration of the above-mentioned data with patient’s clinical characteristics and identification of unknown patterns (biomarkers) associated with responses to ICB, an urgent unmet clinical need. My expertise in melanoma immunology and in the analysis of large clinical datasets will be instrumental for the successful completion of this project.
Champ scientifique
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesearth and related environmental sciencesphysical geographycartography
- medical and health sciencesclinical medicineoncologyskin cancermelanoma
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
9052 ZWIJNAARDE - GENT
Belgique