Fondation pour la Recherche Nuovo Soldati
Grants in cancer research

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Laureates 2023 - 2024

Georges TARRIS
Violaine RANDRIAN
Anthony TURPIN
Alexandre ROUX
Yassine BOUCHOUCHA

Georges TARRIS

Title of the project: Glycosylation patterns in colorectal cancer and potential applications in nanomedicine

Current location: Department of Pathology – University Hospital Francois Mitterrand – Dijon – France
INSERM UMR 1098 « Immunoregulation and Immunopathology Team »
National Reference Center for gastroenteritis viruses (CNRvge)

Fellowship location: Department of Clinical Pathology – University Hospital of Geneva (HUG) - Switzerland

Summary of the project: Colorectal cancer is a major public health issue in European countries. Single-cell RNA sequencing in the epithelial component allowed the characterization of two major subtypes of colorectal cancer i2 and i3, and in addition emphasized the importance of intra-tumor heterogeneity. Furthermore, older studies have suggested an important role for glycosylation in tumorigenesis and tissue invasion. Using formalin-fixed paraffin-embedded tissue samples derived from patients suffering from colorectal cancer, our study aims to identify the glycosylation patterns of the principal tumor types (i.e., i2 and i3). The accurate characterization of specific molecular signatures in tumor cell populations could lead to their use as future biomarkers for precision oncology. The identification of specific glycosylation patterns in cancer stem cells or high-relapsing cells could open new avenues in nanomedicine, for instance the use of Virus-Like Particles derived from human noroviruses, possessing high affinities for Histo-Blood Group Antigens.

Violaine RANDRIAN

Title of the project: Antitumoral immunity induced by hypersensitivity to Interferon gamma

Current location: Poitiers University - Poitiers University Hospital

Fellowship location: Diaz' laboratory, Memorial Sloan Kettering - Cancer Center

Summary of the project: Mismatch repair deficient (MMR-d) colorectal cancers are highly sensitive to immune checkpoint blockade. Anti-tumoral immune response requires favorable immune checkpoint profile, effective antigen presentation and cytokinic environment, among which interferon gamma (IFN) is essential. We aim at deciphering the mechanisms underlying the response to IFN. Using high throughput in vitro IFN assays of multiple MMR-proficient and MMRd models, we will study the landscape of IFN sensitivity across cancers. Combining a multiomic approach, we will identify therapeutic candidates potentially modulating IFN sensitivity and validate the ability of these drugs to induce antitumoral activity in preclinical models.

Anthony TURPIN

Title of the project: PANAM project : « PARP iNhibitors Associated tumour immune Microenvironment changes in PANcreatic ductal AdenocarcinoMa »

Current location:
Oncologue médical MCU-PH dans le Service d’oncologie médicale de l’Hôpital Claude Huriez (CHU de Lille), Rue Michel Polonovski, 59037 Lille Cedex

Associated Research Laboratory: Équipe “Target, Efficacy and resistance to anti-tumor targeted therapies” du laboratoire CANTHER UMR 9020 CNRS - UMR-S 1277 Inserm - Université de Lille - Institut Pasteur de Lille - CHU de Lille- Institut de Biologie de Lille, dirigée par Isabelle Van Seuningen.

Fellowship location: Gastrointestinal and Endocrine Tumors Group - Vall d’Hebron Institute of Oncology, CELLEX CENTER, C/ Natzaret, 115-117, 08035 – BARCELONA – Spain
Professor Teresa Macarulla, MD., PhD

Summary of the project: There is an unmet medical need to seek effective therapeutic strategies for Pancreatic Ductal Adenocarcinoma (PDAC) patients’ management. Recently, encouraging results have been reported in PDAC patients with germline mutations of BRCA1/2 receiving PARP inhibitor olaparib, as maintenance therapy after platinum-based induction chemotherapy. Nonetheless, about 40% of patients displayed primary/secondary resistance to olaparib. We wonder if the tumour immune microenvironment changes are distinct between HR gene-mutated PDAC patients who are sensitive to PARPi and those who are not sensitive. By combining the state-of-the-art multiplexing immunohistochemistry and simultaneously profiling immune repertoire (BCR/TCR) and gene expression at the single-cell level, we propose to deep characterize the evolution of the immune microenvironment in HR gene mutated PDAC patients upon PARPi. The overall objective of our project is to define the best potential therapeutic sequence (i.e before PARPi, in combination, or in case of resistance) in order to design clinical trials.

Alexandre ROUX

Title of the project: Transcriptomic characterization of glial stem cells in glioblastoma, IDH-wildtype. Towards a better understanding of gliomagenesis.

Current location: GHU Paris – Neuro Sainte-Anne, Department of Neurosurgery – Paris Cité University.
The Institute of Psychiatry et Neuroscience of Paris (IPNP), IMA-Brain lab, Neuro-oncology group, UMR 1266 INSERM.

Project location: Montreal Neurological Institute – McGill University – Brain Tumor Research Centre, Montreal, Canada

Summary of the project: Glioblastoma is the most common and the most aggressive primary central nervous system tumor in adults. In France, it is estimated that 3,000 new cases occur annually, and their incidence is increasing. Important obstacles are hindering the development of effective treatments against this disease and in particular its important tumor heterogeneity. It has recently been demonstrated the persistence, after treatment, of glial stem cells whose origin and role are still poorly understood and which would be at the origin of the early recurrence of glioblastoma as well as its resistant to current oncological treatments. We want to establish the transcriptomic signature of isolated cells from peroperative samples of newly diagnosed and recurrent glioblastomas, IDH-wildtype in adults using the SCRNASEQ. We thus want to isolate and sequence the differentiated glial cells, glial stem cells and neural cells in the tumor area, inside the tumor and the subventricular zone in order to better characterize them. This fundamental research work consists in generating a real atlas of the different cancer and healthy cellular lines composing glioblastoma and its environment, during the different stages of the disease, in order to improve our knowledge on the potential mechanisms of resistance to the different known treatments. This work open the perspective of new innovative treatments targeting these different cellular components.

Yassine BOUCHOUCHA

Title of the project: Developmental and immunological disorders in pediatric CNS BCORITD and CNS NB FOXR2 tumors

Current location: Service d’Onco-pédiatrie de l’Institut Curie (Centre SIREDO), Institut Curie, 26 rue d’Ulm 75005 Paris.

Fellowship location: Laboratoire de Pr N. Jabado, Centre de recherche de l’Université Mc Gill (RI-MUHC), Montreal, Canada.

Summary of the project: CNS BCOR-ITD and CNS NB-FOXR2 are newly uncovered deadly embryonal brain tumors with a poor survival. To overcome the limited knowledge on molecular pathways driving and sustaining these tumors, we propose to build a comprehensive multi-omics approach to identify their cell(s)-of-origin and the transcriptional and epigenetic deregulation driving potential developmental arrests underlying their formation and oncogenesis. We will use single-cell spatial and multiomic studies of the transcriptome, open chromatin, and specific epigenetic marks, in association with imaging mass cytometry (IMC), a spatial proteomic approach aimed to further help chart the tumor microenvironment. Integrating data from the transcriptome, epigenome and proteome will provide invaluable information on developmental origins, pathways to tumorigenesis, inter and intratumoral heterogeneity and spatial information on the microenvironment including how immune cells of the host react to the malignant infiltrate in these orphan deadly brain tumor entities. Results from this study have potential to provide novel targets, help design and predict responses to available immunotherapies.