Skip to main content
European Commission logo
français français
CORDIS - Résultats de la recherche de l’UE
CORDIS
CORDIS Web 30th anniversary CORDIS Web 30th anniversary

Fucosylated Clusterin: a novel mechanism of tumor escape from immune response

Objectif

Clusterin (CLU) is a ubiquitous glycoprotein that function as an extracellular chaperone, binding to apoptotic cells and stressed-proteins and preventing the generation of insoluble aggregates. Although CLU is overexpressed in many type of cancers and associated with bad prognosis, the nature of this association remains obscure. It has been previously discovered an isoform of CLU present in seminal plasma that bears fucosylated glycans that confers the ability to bind to DC-SIGN; an endocytic C-type lectin receptor expressed on dendritic cells (DCs) and macrophages (MAC) that has been associated with immunosuppression.
Our preliminary results showed spontaneous regression of tumors in CLU-/- mice after adoptive transfer in 2 models. We also observed that CLU present in breast cancer bears fucosylated glycans with the ability to bind to DC-SIGN.
We hypothesize that tumor fucosylated CLU (Fuc-CLU) promotes immunosuppression by targeting tumor cell-associated antigens to DC-SIGN expressing DCs and MAC, promoting antigen presentation in a tolerogenic context. In this sense, Fuc-CLU could represent a new mechanism of tumor escape from immune response.
The main objectives are: to analyse Fuc-CLU expression pattern and production by tumor and stromal cells; to address the role of Fuc-CLU in immune modulation and tumor cell-associated antigen presentation; and to study the effect of Fuc-CLU on tumor development in an in-vivo model.
The expertise of Dr. Amigorena and Institute Curie represent a major competitive advantage for the project. The results are expected to be published in peer-reviewed journals of high impact (with Open Access whenever possible), communicated in scientific meetings and to society at large. Expected results and deliverables will enhance the knowledge base and excellence of the European Scientific Community in the field anti-tumor immunity. This experience will be a key step for my scientific development to reach an independent position.

Régime de financement

MSCA-IF-EF-ST - Standard EF

Coordinateur

INSTITUT CURIE
Contribution nette de l'UE
€ 173 076,00
Adresse
RUE D ULM 26
75231 Paris
France

Voir sur la carte

Région
Ile-de-France Ile-de-France Paris
Type d’activité
Research Organisations
Liens
Coût total
€ 173 076,00