Descrizione del progetto DEENESFRITPL Uno studio completo sull’attività specifica delle cellule T durante la progressione metastatica del carcinoma mammario Il carcinoma mammario è il secondo cancro più comune per le donne nel mondo. Migliorare la risposta del carcinoma mammario metastatico all’inibizione dei checkpoint immunitari della strategia immunoterapica richiede una migliore comprensione del particolare contesto immunitario. Le cellule T natural killer invarianti (iNKT, invariant Natural Killer T) sono cellule T specializzate che riconoscono gli antigeni lipidici; il potenziale antitumorale di queste cellule non è stato approfondito in quanto sono scarsamente presenti nelle pazienti oncologiche. Il progetto BreaKer, finanziato dall’UE, lavora sull’ipotesi secondo cui la scarsa presenza e la bassa attivazione delle cellule iNKT sono il risultato dei meccanismi immunosoppressori indotti dal cancro. L’obiettivo del progetto è condurre uno studio completo sui meccanismi immunofenotipici e di attivazione delle cellule iNKT nelle pazienti affette da carcinoma mammario metastatico e in soggetti sani, per lo sviluppo di nuove immunoterapie di combinazione dirette a questo tipo di cancro. Mostra l’obiettivo del progetto Nascondi l’obiettivo del progetto Obiettivo Breast cancer is the second cause of cancer-related death in women. Although cancer immunotherapy emerged as a successful therapy for many cancer types, the response of metastatic breast cancer patients to immune checkpoint blockade remains disappointing, urging for a better understanding of the breast cancer immune landscape. iNKT cells are lipid-specific T cells that bridge innate and adaptive immunity and exert a plethora of immune functions depending on tissue distribution. Despite their known antitumor potential, they have been largely overlooked in the cancer field for their content paucity in cancer patients. I hypothesize that their scarce abundance and poor activation status is caused by cancer-induced immunosuppressive mechanisms. Indeed, I observed that circulating and metastasis-infiltrating iNKT cells are functionally impaired in the K14cre;Cdh1F/F;Trp53F/F(KEP)-based mouse model of de novo breast cancer metastases. With a translational approach, I will provide an unprecedented comprehensive dataset comparing iNKT cell immunophenotype in metastatic breast cancer patients and healthy controls. Next, I will generate human iNKT cell lines to perform in vitro mechanistic studies aimed at assessing how cancer-associated inflammation can modulate iNKT cell antitumor activity. Moreover, the innovative use of iNKT cell deficient Jα18-/- mice coupled to the KEP-based model of breast cancer metastases, will offer a clear picture of the role of iNKT cells and their cancer-associated cellular networks during the metastatic cascade. Finally, I will in vivo deplete immunosuppressive cells to unleash iNKT cell antitumor activity. My solid knowledge of iNKT cell biology combined with the expertise in breast cancer-associated inflammation of the hosting lab and the cutting-edge clinical research of the institute will uniquely generate fundamental knowledge with high applicative potential for the design of novel combinatorial immunotherapies for metastatic breast cancer. Campo scientifico natural sciencesbiological sciencescell biologyengineering and technologyelectrical engineering, electronic engineering, information engineeringinformation engineeringtelecommunicationstelecommunications networksmobile networkmedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesbasic medicineimmunologyimmunotherapy Parole chiave iNKT cells Breast cancer metastasis Cancer immunosuppression Myeloid cells Breast cancer patients Genetically engineered mouse models Translational research Programma(i) 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 Argomento(i) MSCA-IF-2020 - Individual Fellowships Invito a presentare proposte H2020-MSCA-IF-2020 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinatore STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS Contribution nette de l'UE € 175 572,48 Indirizzo PLESMANLAAN 121 1066 CX Amsterdam Paesi Bassi Mostra sulla mappa Regione West-Nederland Noord-Holland Groot-Amsterdam Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 175 572,48
