Projektbeschreibung
Die Tumormikroumgebung liefert Hinweise zur Antwort auf die Immuntherapie
Mit Antikörpern, die an negativ regulierenden Immuncheckpoints ansetzen und die antitumorale Immunantwort reaktivieren, werden bei Melanompatientinnen und -patienten vielversprechende klinische Ergebnisse erzielt. Warum jedoch die Lebenszeitverlängerung und gar die vollständige Remission nur bei sehr wenigen Patientinnen und Patienten erreicht werden können, ist weitgehend unklar. Ziel des EU-finanzierten Projekts cellsIMPACT ist die Entdeckung neuartiger und robuster Biomarker zur Vorhersage der Antwort auf die Immun-Checkpoint-Blockade-Therapie. Die Forschenden werden Tumorbiopsien und Blutproben von Melanompatientinnen und -patienten analysieren und nach der Immun-Checkpoint-Blockade-Therapie dynamische Darstellungen der Tumormikroumgebung vornehmen. Durch die Integration dieser Informationen in klinische Daten kann dazu beigetragen werden, die Faktoren des Ansprechens auf eine Immuntherapie zu identifizieren.
Ziel
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.
Wissenschaftliches Gebiet
Not validated
Not validated
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesearth and related environmental sciencesphysical geographycartography
- medical and health sciencesclinical medicineoncologyskin cancermelanoma
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
9052 ZWIJNAARDE - GENT
Belgien