CORDIS - Resultados de investigaciones de la UE
CORDIS

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

Descripción del proyecto

El microentorno tumoral proporciona información sobre la respuesta a la inmunoterapia

Los anticuerpos que actúan contra varios puntos de control negativos del sistema inmunitario y restablecen las respuestas inmunitarias antineoplásicas ofrecen resultados clínicos prometedores para los pacientes con melanoma. Con todo, aún no se comprende por qué la prolongación de la vida, e incluso la remisión completa, se observa únicamente en un pequeño porcentaje de los pacientes. El objetivo del proyecto financiado con fondos europeos cellsIMPACT es descubrir biomarcadores nuevos y precisos para predecir la respuesta a la terapia de bloqueo de los puntos de control del sistema inmunitario. Los investigadores analizarán biopsias de tumores y muestras de sangre de pacientes con melanoma y crearán mapas dinámicos del microentorno tumoral tras la terapia de bloqueo de los puntos de control del sistema inmunitario. La combinación de esta información con datos clínicos ayudará a identificar los factores determinantes del éxito de la inmunoterapia.

Objetivo

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.

Coordinador

VIB VZW
Aportación neta de la UEn
€ 178 320,00
Dirección
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Bélgica

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Región
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Tipo de actividad
Research Organisations
Enlaces
Coste total
€ 178 320,00