Descripción del proyecto
Investigación de la metástasis hepática para mejorar la inmunoterapia
La metástasis hepática es frecuente en varios tipos de cáncer. Si bien las nuevas terapias dirigidas a favorecer la respuesta de los linfocitos T son prometedoras, solo una minoría de los pacientes se beneficia de ellas. Desarrollar nuevas inmunoterapias requiere identificar nuevas células y moléculas. En este sentido, actuar de forma selectiva sobre la respuesta inmunitaria innata ofrece nuevas oportunidades para controlar los tumores. En el proyecto TREATLIVMETS, financiado con fondos europeos, se pretende mejorar la inmunoterapia de la metástasis hepática mediante el estudio de la biología de las células linfoides innatas y las células mieloides. El equipo del proyecto empleará modelos genéticos murinos avanzados y muestras de tejido humano para identificar las interacciones celulares que definen el microentorno tumoral metastásico, investigar las funciones de las células inmunitarias que regulan la metástasis y aprovechar las propiedades antitumorales de las células inmunitarias innatas.
Objetivo
Liver metastases commonly develop in up to 50% of patients with various cancer types. The most common cancer that metastasizes to the liver is colorectal cancer (CRC). At least 25% of CRC patients develop colorectal liver metastases (CRLM) during their illness. CRLM represent the major unmet clinical need for this malignancy, as the 5-year survival rate of patients with unresectable disease does not exceed 2%. New therapies that promote antitumor immunity have been recently developed, mostly focusing on enhancing T cell responses. Although these therapies have led to unprecedented successes, only a minority of patients benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in next generation immunotherapies. Given the crucial role of innate immune responses in immunity, targeting these responses opens up new possibilities for tumour control. We hypothesize that the immunotherapy of liver metastases can be significantly improved through harnessing the biology of innate lymphoid cells (ILC), such as Natural Killer (NK) cells and ILC1s, and myeloid cells such as macrophages and DCs.
Our team brings together experts in the biology of tissue-resident myeloid (Ginhoux, PI4) and lymphoid (Gasteiger, cPI) cells, in liver immunology (Fumagalli, PI3), and in the development of novel immunotherapeutic strategies that modulate immune cells in the fight against cancer (Vivier, PI2). By combining cutting-edge single cell and spatial transcriptomics of human patient samples with cross-species analyses in advanced genetic mouse models, we aim
(1) to identify cellular interactions defining the metastatic tumor microenvironment across murine and human tissue-specimens,
(2) to investigate immune cell functions regulating metastatic disease using a unique combination of advanced genetic mouse and human tissue models, and
(3) to harness the anti-tumoral functions of innate immune cells via next generation cell engagers.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC-SYG - HORIZON ERC Synergy GrantsInstitución de acogida
97070 Wuerzburg
Alemania