10 / 08 / 2023
Cancers (Basel)
Multi-Institutional Evaluation of Pathologists’ Assessment Compared to Immunoscore
Joseph Willis, Robert A Anders, Toshihiko Torigoe, Yoshihiko Hirohashi, Carlo Bifulco, Inti Zlobec, Bernhard Mlecnik,..., Franck Pagès, Alessandro Lugli, Jérôme Galon
The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists' visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists' T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS....
02 / 08 / 2023
Clinical epigenetics
DNA hypermethylation driven by DNMT1 and DNMT3A favors tumor immune escape contributing to the aggressiveness of adrenocortical carcinoma
Gwenneg Kerdivel, Floriane Amrouche, Marie-Ange Calmejane, Floriane Carallis, Juliette Hamroune, Constanze Hantel, Jérôme Bertherat, Guillaume Assié, Valentina Boeva
Adrenocortical carcinoma is rare and aggressive endocrine cancer of the adrenal gland. Within adrenocortical carcinoma, a recently described subtype characterized by a CpG island methylator phenotype (CIMP) has been associated with an especially poor prognosis. However, the drivers of CIMP remain unknown. Furthermore, the functional relation between CIMP and poor clinical outcomes of patients with adrenocortical carcinoma stays elusive. Here, we show that CIMP in adrenocortical carcinoma is linked to the increased expression of DNA methyltransferases DNMT1 and DNMT3A driven by a gain of gene copy number and cell hyperproliferation. Importantly, we demonstrate that CIMP contributes to tumor aggressiveness by favoring tumor immune escape. This effect could be at least partially reversed by treatment with the demethylating agent 5-azacytidine.
21 / 07 / 2023
iScience
IFITM1 inhibits trophoblast invasion and is induced in placentas associated with IFN-mediated pregnancy diseases
Séverine A Degrelle, Julian Buchrieser, Anne Dupressoir, Françoise Porrot, Laurence Loeuillet, Olivier Schwartz, Thierry Fournier
Interferon-induced transmembrane proteins (IFITMs) are restriction factors that block many viruses from entering cells. High levels of type I interferon (IFN) are associated with adverse pregnancy outcomes, and IFITMs have been shown to impair the formation of syncytiotrophoblast. Here, we examine whether IFITMs affect another critical step of placental development, extravillous cytotrophoblast (EVCT) invasion. We conducted experiments using in vitro/ex vivo models of EVCT, mice treated in vivo with the IFN-inducer poly (I:C), and human pathological placental sections....
06 / 07 / 2023
Journal of cystic fibrosis
Airway infections as a risk factor for Pseudomonas aeruginosa acquisition and chronic colonisation in children with cystic fibrosis
Julie Mésinèle, Manon Ruffin, Loïc Guillot, Pierre-Yves Boëlle, Harriet Corvol
Pseudomonas aeruginosa (Pa) infection is detrimental to people with cystic fibrosis (pwCF). Several clinical and genetic factors predispose to early Pa infections. However, the role of earlier infections with other pathogens on the risk of Pa infection in paediatric pwCF remains unknown. Using Kaplan-Meier method, we computed the cumulative incidences of bacterial and fungal initial acquisition (IA) and chronic colonisation (CC) in 1,231 French pwCF under 18 years of age for methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA), Stenotrophomonas maltophilia, Haemophilus influenzae, Achromobacter xylosoxidans, and Aspergillus species. Previous infections were analysed as Pa-IA and Pa-CC risk factors using Cox regression models...
29 / 06 / 2023
The european journal of Neuroscience
Bayesian multilevel hidden Markov models identify stable state dynamics in longitudinal recordings from macaque primary motor cortex
Sebastien Kirchherr, Sebastian Mildiner Moraga, Gino Coudé, Marco Bimbi, Pier F Ferrari, Emmeke Aarts, James J Bonaiuto
Neural populations, rather than single neurons, may be the fundamental unit of cortical computation. Analysing chronically recorded neural population activity is challenging not only because of the high dimensionality of activity but also because of changes in the signal that may or may not be due to neural plasticity. Hidden Markov models (HMMs) are a promising technique for analysing such data in terms of discrete latent states, but previous approaches have not considered the statistical properties of neural spiking data, have not been adaptable to longitudinal data, or have not modelled condition-specific differences....
27 / 06 / 2023
Proteogenomic Characterization of Bladder Cancer Reveals Sensitivity to Apoptosis Induced by Tumor Necrosis Factor-related Apoptosis-inducing Ligand in FGFR3-mutated Tumors
Clarice S Groeneveld, Virginia Sanchez-Quiles, Florent Dufour, Mingjun Shi,..., Aurélien de Reyniès, Isabelle Bernard-Pierrot, François Radvanyi
Molecular understanding of muscle-invasive (MIBC) and non-muscle-invasive (NMIBC) bladder cancer is currently based primarily on transcriptomic and genomic analyses. To conduct proteogenomic analyses to gain insights into bladder cancer (BC) heterogeneity and identify underlying processes specific to tumor subgroups and therapeutic outcomes. Proteomic data were obtained for 40 MIBC and 23 NMIBC cases for which transcriptomic and genomic data were already available. Four BC-derived cell lines harboring FGFR3 alterations were tested with interventions...
