Objective 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. Fields of science medical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2017 - Individual Fellowships Call for proposal H2020-MSCA-IF-2017 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator INSTITUT CURIE Net EU contribution € 173 076,00 Address RUE D ULM 26 75231 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 173 076,00