Laureates 2025 - 2026
Marc HILMIMathieu ROULEAUX DUGAGE
Elisa GOBBINI
Nikolaus DEIGENDESCH
Jean PINSON
Juan Francisco GRAU BEJAR
Marc HILMI
Title of the project: Resistance and response to combined inhibition of PARP and PD-1 in pancreatic ductal adenocarcinoma: an ancillary study of the POLAR trial.
Current location: Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, USA.
Summary of the project: Pancreatic ductal adenocarcinoma (PDAC) is a major public health concern due to its increasing incidence and poor prognosis. The project is part of the POLAR clinical trial, which evaluates the efficacy of combined PARP and PD-1 inhibition in patients with PDAC harboring homologous recombination deficiency gene mutations. This study aims to identify mechanisms of resistance and response to this treatment by analyzing the tumor microenvironment and cancer-associated fibroblasts. Advanced technologies such as single-cell RNA sequencing and multiplex immunofluorescence will be used to decipher tumor-immune-stromal interactions and uncover new therapeutic targets. The findings will enhance our understanding of PDAC biology and contribute to the development of novel strategies to improve patient outcomes.
Mathieu ROULEAUX DUGAGE
Title of the project: Impact of EZH2 inhibitors on the anti-tumor immune response.
Current place of work: DITEP, Institut Gustave Roussy, Villejuif, France
Fellowship location: Prof. Sergio Quezada’s laboratory, University College London, United Kingdom
Summary of the project: Epigenetics plays a crucial role in regulating the immune system and tumor progression. EZH2 inhibitors, targeting the Polycomb Repressive Complex 2 (PRC2), have shown promising therapeutic potential in oncology, particularly in SWI/SNF-deficient solid tumors. However, their impact on tumor-immune interactions remains poorly understood.
This project is based on the analysis of samples collected from the basket trial EZHiSWITCH (treatment with Valemetostat in patients with SWI/SNF-deficient tumors). Tumor and blood samples will be collected before and after treatment to conduct transcriptomic (scRNAseq, TCR sequencing, ATACseq) and immunological (soluble factor quantification, flow cytometry) analyses. Bioinformatics analysis of the data will be used to assess the immunomodulatory effects of EZH2 inhibitors by studying their influence on type I IFN signaling, neoantigen expression, and T cell polarization.
Elisa GOBBINI
Title of the project: To identify immunotherapy responders among lung cancer patients by multiomic integration
Old place of work: Curie Institute, Oncology Departement, Paris
Current place of work: Sen Lab, Mount Sinai, Sciences Departement, New York
Summary of the project: Immunotherapy have radically change lung cancer management but the main challenge remains to identify responder patients and determine the mechanisms of resistance in non-responders in order to offer a more personalized treatment strategy. New emerging biomarkers includes bulky transcriptomic tumor signatures, spatial transcriptomic analysis of tumor microenvironment and radiomics. Multimodal prediction models seems to outperform unimodal measures but large datasets are needed to confirm these results.
Our aim is to optimize current standard-of-care in lung cancer management, integrating clinical, molecular, spatial transcriptomic and radiological data to identify a multiomics integrative signature able to predict response to immunotherapy. To do that we will take advantage from a large cohort of lung cancer patients that have been analyzed by a multiomic approach providing a unique dataset for integrative analysis.
This project will provide useful information to inform future clinical trials allowing the identification of new potential targets in lung cancer.
Nikolaus DEIGENDESCH
Title of the project: Deep MS-based proteomics of non-small cell lung cancer (NSCLC)
Current location: Institute of Pathology, University Hospital Basel, Switzerland
Fellowship location: Institute of Innate Immunity, Department of Systems Immunology and Proteomics, University of Bonn, Germany
Summary of the project: Lung cancer is the most prevalent malignancy worldwide and a leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) as the most common subtype. Despite advances in identifying genetic alterations, many patients still lack effective therapeutic targets, and the reasons for poor treatment responses remain unclear. Next-generation sequencing (NGS) often fails to identify numerous genetic alterations and to predict clinical outcomes accurately. In contrast, proteins that regulate key biological processes provide valuable insights into tumor biology beyond genetic data.
This research project aims to explore NSCLC using spatial tissue proteomics, a cutting-edge technology to analyze proteomic signatures in tumor tissue. By using formalin-fixed paraffin-embedded (FFPE) tissue samples from patients and analyzing different histomorphological regions, we aim to uncover tumor heterogeneity and to understand the tumor microenvironment's impact on disease progression and therapy response. Machine learning-based image analyses will be used to identify regions of interest for subsequent proteomic analyses. Additionally, ultra-sensitive proteomics of cytological specimens will be applied to track tumor evolution under treatment, to better understand mechanisms of secondary resistance.
We envision that deep characterization of tumor proteomes will lead to the identification of novel and complex biomarkers for precision oncology, ultimately improving patient outcomes.
Jean PINSON
Title of the project: Clinical and Scientific Fellowship within the International Reference Center for the Management of Locally Advanced or Recurrent Pelvic Cancers, with an Evaluation of the Benefits of Preoperative 3D Reconstruction
Current place of work: Department of Digestive and Oncological Surgery - Rouen University Hospital - 1 rue de Germont 76031 Rouen, France
Fellowship location: Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia, headed by Pr Michael Solomon.
Summary of the project: Each year, 14,000 new cases of rectal cancer are diagnosed in France, of which 5 to 10% are locally advanced. After surgery, approximately 10% of patients will experience a local recurrence. These locally advanced or recurrent tumors have a grim prognosis without surgical intervention. However, an R0 resection (i.e., resection with clear margins) can significantly improve five-year survival, reaching 50 to 60%. Achieving an R0 resection often requires complex surgery involving adjacent organs (bone, vessels, nerves) and a multidisciplinary approach. Moreover, 3D reconstruction allows for a better understanding of the spatial relationships between the tumor and adjacent structures, with numerous potential applications. The purpose of this mobility is to gain experience and develop new skills regarding the indications, techniques, and perioperative management of patients with locally advanced or recurrent tumors. The project includes a prospective evaluation of the impact of 3D reconstruction on perioperative outcomes. It also involves developing an automatic segmentation algorithm to facilitate the routine clinical use of 3D reconstruction. In collaboration with the Surgical Outcomes Research Centre (SOuRCe), this project aims to enhance surgical procedures while integrating an educational and scientific dimension. The expected outcomes could transform the management of advanced pelvic cancers, thereby reinforcing the importance of expert centers and emerging technologies in improving patient care.
Juan Francisco GRAU BEJAR
Title of the project: Mismatch Repair-deficient Endometrial Cancer Microenvironment Analysis: Prediction of Resistance to Immune Checkpoint Inhibitors and Exploration of Reversing Strategies
Current place of work: Vall d'Hebron Institute of Oncology, Barcelone, Espagne
Fellowship location: Institut Gustave Roussy, Villejuif, France
Summary of the project: Endometrial cancer is a common malignancy, particularly in postmenopausal women, with limited treatment options in advanced stages. While immune checkpoint inhibitors have shown efficacy in mismatch repair-deficient (MMRd) endometrial cancer, many patients develop resistance. This study investigates the role of the tumor microenvironment in driving resistance to immunotherapy and explores strategies to overcome it. Using multiplexed spatial immune profiling, Second Harmonic Generation microscopy, and high-throughput mass spectrometry, we previously identified key microenvironmental predictors of resistance. The current project aims to validate these findings in an independent cohort from a prospective clinical trial and develop preclinical models to study immune evasion mechanisms. By identifying novel resistance biomarkers and refining patient selection, this research seeks to enhance immunotherapy efficacy and develop innovative therapeutic strategies, with potential implications for other MMRd malignancies, such as colorectal cancer.