A "Lymphocyte MicroRNA Signature" as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming
CANCERS
Authors: Incorvaia, Lorena; Fanale, Daniele; Badalamenti, Giuseppe; Brando, Chiara; Bono, Marco; De Luca, Ida; Algeri, Laura; Bonasera, Annalisa; Corsini, Lidia Rita; Scurria, Salvatore; Iovanna, Juan Lucio; Russo, Antonio; Bazan, Viviana
Abstract
Simple Summary MicroRNAs are small molecules of non-coding RNAs which regulate gene expression at the post-transcriptional level. Normal miRNA expression and function can be deregulated in cancer. The comprehensive molecular characterization of Renal Cell Carcinoma shows several genes silenced and signaling pathways deregulated by epigenetic modifications, such as the abnormal expression of miRNAs. They can be secreted from malignant cells in whole-blood, plasma, serum, and urine samples, making miRNAs potential non-invasive tumor biomarkers. However, if a single miRNA can show low discriminatory power, the combination of miRNAs in a "miRNA signature", identified in the peripheral lymphocytes of patients, could function better with much higher probability to predict the response to immunotherapy and to discriminate responders from non-responders patients already at therapy baseline. Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called "lymphocyte miRNA signature", specifically induced in long-responder patients (CR, PR, or SD to nivolumab >18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients.
Faeces - Urine separation via settling and displacement: Prototype tests for a novel non-sewered sanitation system
SCIENCE OF THE TOTAL ENVIRONMENT
Authors: Hennigs, Jan; Ravndal, Kristin T.; Parker, Alison; Collins, Matt; Jiang, Ying; Kolios, Athanasios J.; McAdam, Ewan; Williams, Leon; Tyrrel, Sean
Abstract
The development of novel, non-sewered sanitation systems like the Nano Membrane Toilet requires thorough investigation of processes that may seem well-understood. For example, unlike the settling of primary sludge, the separation of solids from liquids in a small-volume container at the scale of a household toilet has not been studied before. In two sets of experiments, the settling of real faeces and toilet paper in settling columns and the settling of synthetic faeces in a conical tank are investigated to understand the factors affecting the liquid quality for downstream treatment processes. Toilet paper is found to be a major inhibitor to settling of solids. While a lower overflow point results in better phase separation through displacement of liquid, a higher overflow point and frequent removal of solids may be more advantageous for the liquid quality. (C) 2020 The Authors. Published by Elsevier B.V.