Institute Curie

Our systematic and comprehensive genomic and spatially resolved profiling of Hodgkin lymphoma revealed a paradigmatic link between a genetic disease subtype and TME composition and function. Insights into mutation-driven mechanisms of deregulated cytokine signaling will pave the way for therapeutic interventions that interfere with oncogenic signaling and cellular ecosystems in cancer.

Abstract Introduction and aims Cutaneous exposure to food allergens prior to oral exposure has been associated with sensitization and the development of food allergies (Lack 2008). Similarly, the prevalence of food allergies has been linked to the frequency of massage in babies (Perkin et al. 2021). However, the mechanism by which environmental food allergens come into contact with the immune cells responsible for sensitization in the skin or how skin massage may facilitate this process is currently unknown. This study aimed to investigate whether massage-induced skin stretching facilitated the percutaneous permeation of food allergens into the skin. Methods Hydrophilic and hydrophobic proteins were extracted from raw and roasted peanuts and fluorescently labelled with Sulfo Cyn5 NHS ester. Franz diffusion cells mounted with full-thickness mice skin (Balb/C, 8–12 weeks old) were employed to assess the skin penetration of the peanut proteins with [stretch (+)] and without [stretch (−)] skin stretching. Results Peanut roasting led to significant changes in the peanut protein composition compared with raw peanuts with hydrophilic protein Ara h −1 aggregate formation and reduced hydrophobic olesion and caleosin protein levels. When applied to the tissue without stretching, a small amount of the peanut protein passed into and through the tissue regardless of peanut type or processing. However, stretching increased the peanut penetration of all the extracts applied to the skin. The raw hydrophilic and roasted hydrophobic peanut extracts showed the most extensive tissue penetration at 9.5 ± 8.4 µg cm−2 and 7.2 ± 5.9 µg cm−2, respectively. Conclusions Increasing skin tension by 4–5 fold, akin to the skin stretching experienced during baby massage, enhances percutaneous permeation of peanut proteins into the skin. Therefore, skin stretching may contribute to the process of cutaneous allergen sensitization. Further work is needed to understand the clinical relevance of hydrophilic, hydrophobic and aggregated peanut proteins entering the skin during stretching.

Ewing sarcoma (ES) is an aggressive sarcoma with a peak incidence in adolescents and young adults. Current therapy involves multiagent chemotherapy and local therapy but despite intensification of treatment patients with metastases at diagnosis and recurrent disease have poor prognosis. Improved understanding of ES biology has identified novel targets with promising activity in ES patients. Tyrosine kinase inhibitors are currently being evaluated as combination and maintenance therapy. Other emerging therapies include those that target the EWSR1:FLI1 fusion oncoprotein, cell cycle, apoptotic and DNA-repair pathways. Immunotherapeutic approaches are also being investigated, particularly CAR-T and CAR-NK cell therapy. Close collaboration between clinicians and biologists has also highlighted the importance of biomarkers that are still being validated prospectively and might be incorporated into standard of care in the future.

The Rho family GTPases RhoA, Rac1 and Cdc42 are well established regulators of collective migration by driving the formation of cellular protrusions and by regulating actomyosin contraction and adhesion. However, how their activation and inhibition are spatially and temporally coordinated in vivo remains unclear. Using GFP knock-in lines, we systematically characterised the localization patterns of all Drosophila RhoGEFs (activators) and RhoGAPs (inhibitors) in border cells, a model of collective migration. We have further combined RNAi screening with GFP-based validation of depletion efficiency to assess the functional significance of those RhoGEF/GAPs expressed in border cells. This identified RhoGAP15B as a localized inhibitor of RhoA activity at the border cell cortex. RhoGAP15B regulates cluster morphology and is enriched at the leading cell front, where it restrains actomyosin contractility to promote protrusive behaviour. Our findings reveal RhoGAP15B as a key spatial RhoA regulator and highlight that patterned RhoGAP and RhoGEF activities are essential for coordinating cortical contraction and protrusion dynamics during collective migration.

This study tackles the challenge of developing reliable prognostic models for time-to-event (TTE) outcomes using high-dimensional omics data in head and neck cancers. Resampling methods, particularly nested cross-validation, are considered as standard for model hyperparameter selection and performance evaluation. When handling clustered data, balancing the random partition of the cross-validation folds to minimize optimism bias and instability could be tested. This work compares the performance of three nested cross-validation implementations, including random assignment of the folds, clustering-based resampling, and internal-external validation using an hold out approach. We analyzed two head and neck squamous cell carcinoma (HNSCC) cohorts: The Cancer Genome Atlas (TCGA) and SCANDARE (NCT03017573), with clinical data and transcriptomic data normalized as log-transcripts per million. Three model selection methods LASSO, IPF-Lasso, and Priority-LASSO were evaluated within five nested cross-validation frameworks: Standard nested cross-validation, Clustering-based nested-cross validation, nested-cross validation with Combat correction, Nested cross-validation for optimization combined with hold-out for validation, Nested cross-validation for optimization combined with hold-out and ComBat correction for validation. Predictive performance was assessed using 3-year AUC and Integrated Brier Score (IBS). We analyzed data from 581 patients (mean age 61.0 years, 33.6% female) across TCGA-HNSC (n = 505) and SCANDARE (n = 76). Clustering analyses, using UMAP and k-means, identified three transcriptomic clusters. Validation strategies demonstrated reduced instability for Lasso (p < 0.001), IPF-Lasso (p < 0.001) and Priority-lasso (p < 0.001) without apparent optimism in discrimination and calibration metrics with stratified nested cross-validation (SNCV), supporting its utility. As an application using IPF-Lasso Cox models with SNCV, we integrated clinical and transcriptomic data, selecting 35 prognosis variables of head and neck carcinomas. This model achieved a 3-year AUC of 0.71 and IBS of 0.08. Clustering-based nested cross-validation combined with stratified cross-validation offers a robust compromise for developing high-dimensional survival models and evaluating their predictive performance. This approach leverages clustering-derived stratification to balance heterogeneity in the dataset within cross-validation folds, although the training and test sets remain derived from the pooled dataset rather than fully independent cohorts.

BackgroundPatients treated for rare ovarian germ cell tumors (GCT) and sex cord stromal tumors (SCST) often experience long-term survival. Treatments include surgery with or without chemotherapy (CT), which can cause late side effects that negatively impact quality of life (QoL). This study assessed long-term QoL among GCT and SCST survivors compared to age-matched healthy women (HW), focusing on patients treated with CT.MethodsCancer-free GCT and SCST survivors (≥ 2 years post-treatment) were recruited from the INCa French Network TMRG. HW were recruited via the “Seintinelles” platform. Participants completed validated questionnaires assessing QoL (FACT-G/FACT-O), fatigue (MFI), anxiety/depression (HADS), insomnia (ISI), neurotoxicity (FACT/GOG-NTX), cognition (FACT-COG), and sexuality (FACT-O OCS). Clinically relevant differences were defined as ≥ 5% between groups.ResultsA total of 144 survivors (99 GCT and 45 SCST) were included and compared with 284 matched HW (median age: 35.2 years). The median time from the end of treatment was 6 years [Q1 3.5–Q3 9.3]. At inclusion, 42% of patients were menopausal compared to 17% of HW (p < 0.001), with reduced sexual QoL. Survivors reported more cognitive impairment (32% vs. 21%, p = 0.025) and severe neurotoxicity (23% vs. 8%, p < 0.001). QoL, fatigue, anxiety/depression, and insomnia scores were similar for patients and HW.ConclusionsWith a median of 6 years after CT, most GCT and SCST survivors reported similar overall QoL compared to HW but faced premature menopause, reduced sexual QoL, and persistent cognitive and neurotoxic effects.Trial registration numberNCT03418844.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04540-x.