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Understanding resistance to immune checkpoint inhibitors by mapping the tumor-host ecosystem at single-cell resolution

Project description

The tumour microenvironment provides cues for immunotherapy response

Antibodies that target various negative immune regulatory checkpoints and restore anti-tumour immune responses offer promising clinical outcomes for melanoma patients. However, why life extension and even complete remission is seen in only a small percentage of patients is poorly understood. The EU-funded cellsIMPACT project aims to discover novel and robust biomarkers predicting response to immune checkpoint blockade (ICB) therapy. Researchers will analyse tumour biopsies and blood samples from melanoma patients and establish dynamic maps of the tumour microenvironment following ICB therapy. The integration of this information with clinical data will help identify the determinants of immunotherapy success.


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.


Net EU contribution
€ 178 320,00

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Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Total cost
€ 178 320,00