October 2022 - : PhD Student at IREC UCLouvain
October 2020 - June 2022 : Master of Biomedical sciences - specialization in oncology (UCLouvain)
October 2016 - June 2020 : Bachelor of Biomedical sciences (UCLouvain)
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Immunology, Computer Science
7
Scopus Publications
Scopus Publications
TREX1, a predator for treating MSI-H tumors? Elena Benidovskaya, Joséphine Deneft, Marc Van den Eynde Molecular Oncology, 2026 Immunotherapy has revolutionized cancer treatment; yet, a subset of patients with microsatellite instability‐high (MSI‐H) tumors fails to respond to treatment despite their elevated tumor mutational burden and immunogenic potential. In a recent study, Xu et al . uncover a key mechanism of immune evasion in MSI‐H tumors mediated by the exonuclease TREX1, which degrades cytosolic DNA and suppresses activation of the cyclic GMP‐AMP synthase—stimulator of interferon genes (cGAS‐STING)—type I interferon pathway. Loss of TREX1 restores cytosolic DNA sensing, promotes CD8 + T and NK cell infiltration, and enhances antitumor immunity. These findings highlight TREX1 as a potential therapeutic target to overcome resistance to immune checkpoint blockade.
Response to neoadjuvant chemotherapy in early breast cancers is associated with epithelial–mesenchymal transition and tumor-infiltrating lymphocytes Françoise Derouane, Jérôme Ambroise, Cédric van Marcke, Mieke Van Bockstal, Martine Berlière, Christine Galant, Hélène Dano, Médina Lougué, Elena Benidovskaya, Guy Jerusalem, Vincent Bours, Claire Josse, Jérôme Thiry, Aurélie Daumerie, Caroline Bouzin, Cyril Corbet, François P. Duhoux Molecular Oncology, 2025 Epithelial–mesenchymal transition (EMT) and tumor‐infiltrating lymphocytes (TILs) play a central role in early‐stage breast cancer (BC) and are associated with chemoresistance, stemness, and invasion. The objective of this study was two fold: (a) by investigating the predictive value of EMT and TILs, we aimed to estimate the chance of achieving a response after neoadjuvant chemotherapy (NAC) and (b) to evaluate the potential changes of EMT and TILs in BC upon NAC. Using bulk RNA sequencing and immunofluorescence (IF) for EMT (E‐cadherin and vimentin) and lymphocyte markers (CD3, CD8, FOXP3), we analyzed pre‐ and post‐NAC tumor samples from 100 early‐BC patients treated with NAC. For each BC molecular subtype, we compared the expression of EMT and TILs, at the RNA and protein level, between responding and non‐responding tumors. Paired analysis of pre‐ and post‐NAC samples was performed for patients with residual disease after NAC. RNA sequencing of pre‐ and post‐NAC samples identified significant differences in EMT‐related and inflammation‐related gene expression between non‐responding (RCB‐II/III) and responding (RCB‐0/I) tumors. Increased EMT‐related marker expression was observed after NAC in cases with residual disease, in particular in the luminal subtype. Characterization of TILs in pre‐NAC samples showed substantially more CD3 + CD8‐FOXP3‐lymphocytes in responding HER2+ tumors compared with non‐responding. Paired analyses of pre‐ and post‐NAC samples demonstrated higher levels of CD3 + CD8 + FOXP3‐lymphocytes in residual luminal and triple‐negative BC and higher levels of CD3 + CD8‐FOXP3‐lymphocytes in residual triple‐negative BC compared with other subtypes of lymphocytes. We found that there is an unmet clinical need for reliable biomarkers to predict response to NAC in BC. Our results suggest that an upregulation of the EMT gene signature in diagnostic biopsies is associated with poor response to NAC in early BC, across all subtypes. Additionally, changes in EMT and in the TIL population occur in residual tumors after NAC. These findings could help to personalize future NAC and adjuvant treatment regimens.
Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan Nicolas Huyghe, Elena Benidovskaya, Tariq Masoodi, Isabelle Sinapi, Astrid De Cuyper, Fazulur Vempalli, Simon Beyaert, Caroline Bouzin, Finoula Maestre Osorio, Luigi Ferraro, Nicolas van Baren, Raphaël Helaers, Pierre Goffette, Benoit Ghaye, Aline van Maanen, Marie-Laure Castella, Michele Ceccarelli, Davide Bedognetti, Jérôme Galon, Wouter R.L. Hendrickx, Javier Carrasco, Marc Van den Eynde Cell Reports Medicine, 2025 The treatment of patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) remains a significant clinical challenge. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), induces immunogenic cell death, potentially synergizing with immune checkpoint inhibitors. The phase 2, proof-of-concept, single-arm AVETUXIRI trial (ClinicalTrials.gov: NCT03608046) evaluates the safety and efficacy of cetuximab, irinotecan (a topoisomerase I inhibitor), and avelumab (an anti-programmed cell death ligand 1 [PD-L1]) in 57 patients with RAS wild-type or mutated MSS mCRC refractory to chemotherapy and anti-EGFR mAbs. Exploratory objectives include investigating the tumor immune microenvironment within mCRC biopsies performed during the trial and correlating it with treatment activity. A manageable safety profile is observed. Although the overall efficacy endpoints are not met, biomarkers associated with clinical efficacy are identified. Patients exhibiting a high Immunoscore, strong cytotoxic and T cell proximity to tumor cells, and a high genetic immunoediting score within mCRC biopsies before treatment demonstrate significant therapeutic survival benefit, independent of RAS tumor mutation status.
Multiplex Immunofluorescence Combined with Spatial Image Analysis for the Clinical and Biological Assessment of the Tumor Microenvironment Nicolas Huyghe, Elena Benidovskaya, Simon Beyaert, Aurélie Daumerie, Finoula Maestre Osorio, Frank Aboubakar Nana, Caroline Bouzin, Marc Van den Eynde Journal of Visualized Experiments, 2023 The tumor microenvironment (TME) is composed of a plethora of different cell types, such as cytotoxic immune cells and immunomodulatory cells. Depending on its composition and the interactions between cancer cells and peri-tumoral cells, the TME may affect cancer progression. The characterization of tumors and their complex microenvironment could improve the understanding of cancer diseases and may help scientists and clinicians to discover new biomarkers. We recently developed several multiplex immunofluorescence (mIF) panels based on tyramide signal amplification (TSA) for the characterization of the TME in colorectal cancer, head and neck squamous cell carcinoma, melanoma, and lung cancer. Once the staining and scanning of the corresponding panels are completed, the samples are analyzed on an image analysis software. The spatial position and the staining of each cell are then exported from this quantification software into R. We developed R scripts that allow us not only to analyze the density of each cell type in several tumor compartments (e.g. the center of the tumor, the margin of the tumor, and the stroma) but also to perform distance-based analyses between different cell types. This particular workflow adds a spatial dimension to the classical density analysis already routinely performed for several markers. mIF analysis could allow scientists to have a better understanding of the complex interaction between cancer cells and the TME and to discover new predictive biomarkers of response to treatments, such as immune checkpoint inhibitors, and targeted therapies.
Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine Nicolas Huyghe, Elena Benidovskaya, Philippe Stevens, Marc Van den Eynde Cancers, 2022 Immune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, for colorectal cancer (CRC), ICIs are only approved for the treatment of Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For the vast majority of CRC, that are not dMMR/MSI-H, ICIs alone provide limited to no clinical benefit. This discrepancy of response between CRC and other solid cancers suggests that CRC may be inherently resistant to ICIs alone. In translational research, efforts are underway to thoroughly characterize the immune microenvironment of CRC to better understand the mechanisms behind this resistance and to find new biomarkers of response. In the clinic, trials are being set up to study biomarkers along with treatments targeting newly discovered immune checkpoint molecules or treatments combining ICIs with other existing therapies to improve response in MSS CRC. In this review, we will focus on the characteristics of response and resistance to ICIs in CRC, and discuss promising biomarkers studied in recent clinical trials combining ICIs with other therapies.
