Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.     

Circulating prostaglandin E2: a novel potential prognostic biomarker in patients with hepatocellular carcinoma

Clinical and Experimental Medicine - We aimed to explore the activation of monoacylglycerol lipase (MAGL)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis in hepatocellular carcinoma (HCC),...     

Surgical extrusion: A dental technique

This article describes a technique for surgically extruding severely compromised roots needing prosthetic rehabilitation. Unlike previously described approaches, the technique does not require advanced clinical skills or equipment, may reduce the risk of tooth or bone fracture during the luxation maneuvers, and does not seem to interfere with the alveolar socket healing process.     

In‐Depth Analysis of Hyaline Fibromatosis Syndrome Frameshift Mutations at the Same Site Reveal the Necessity of Personalized Therapy

Hyaline fibromatosis syndrome is an autosomal recessive disease caused by mutations in ANTXR2, a gene involved in extracellular matrix homeostasis. Sixty percent of patients carry frameshift mutations at a mutational hotspot in exon 13. We show in patient cells that these mutations lead to low ANTXR2 mRNA and undetectable protein levels. Ectopic expression of the proteins encoded by the mutated genes reveals that a two base insertion leads to the synthesis of a protein that is rapidly targeted to the ER‐associated degradation pathway due to the modified structure of the cytosolic tail, which instead of being hydrophilic and highly disordered as in wild type ANTXR2, is folded and exposes hydrophobic patches. In contrast, one base insertion leads to a truncated protein that properly localizes to the plasma membrane and retains partial function. We next show that targeting the nonsense mediated mRNA decay pathway in patient cells leads to a rescue of ANTXR2 protein in patients carrying one base insertion but not in those carrying two base insertions. This study highlights the importance of in‐depth analysis of the molecular consequences of specific patient mutations, which even when they occur at the same site can have drastically different consequences.