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CORDIS

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

Descrizione del progetto

Il microambiente tumorale fornisce spunti per la risposta immunoterapica

Anticorpi aventi come target vari punti di controllo immunologici negativi per la regolazione che ripristinano le risposte immunitarie antitumorali offrono risultati clinici promettenti per i pazienti affetti da melanoma. Tuttavia, il motivo per cui un reale allungamento della prospettiva di vita e persino la remissione completa siano osservati solo in una piccola percentuale di pazienti è poco compreso. Il progetto CellIMPACT, finanziato dall’UE, è volto a scoprire nuovi e solidi biomarcatori in grado di prevedere la risposta alla terapia di inibizione del punto di controllo immunitario (ICB, immune checkpoint blockade). I ricercatori analizzeranno le biopsie tumorali e i campioni ematici dei pazienti affetti da melanoma e realizzeranno mappe dinamiche del microambiente tumorale in seguito alla somministrazione della terapia ICB. L’integrazione di queste informazioni con i dati clinici contribuirà a identificare i fattori determinanti del successo dell’immunoterapia.

Obiettivo

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.

Coordinatore

VIB VZW
Contribution nette de l'UE
€ 178 320,00
Indirizzo
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgio

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Regione
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 178 320,00