12:00 – 12:30 Paula Izquierdo

Extracellular vesicles from mesenchymal stem cells reduce neuroinflammation and restore cognitive and motor function in hyperammonemic rats.

Chronic hyperammonemia, a main contributor to hepatic encephalopathy, leads to neuroinflammation which alters neurotransmission leading to cognitive impairment. Currently there are no specific treatments for the neurological alterations in hepatic encephalopathy. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) reduce neuroinflammation in some pathological conditions.
The aim of this work was to assess if treatment of hyperammonemic rats with EVs from MSCs reduces neuroinflammation, improves neurotransmission in hippocampus and cerebellum and restores cognitive and motor function and to study the mechanisms involved.
Treatment of EVs from MSCs was performed in vivo by i.v. injection and ex vivo in hippocampal and cerebellar slices from hyperammonemic or control rats. Hyperammonemia induced neuroinflammation in hippocampus and cerebellum and impaired learning, memory and motor coordination in the tests performed (object location and recognition, Y maze, radial maze and beam walking). Treatment with EVs reduced microglia and astrocytes activation, NF-kB activation and restored performance of hyperammonemic rats in all the behavioral tests. Studies adding EVs to slices ex vivo showed that these beneficial effects were dependent on TGFβ contained in the EVs, which reduced NF-kB activation and the subsequent neuroinflammation.
Conclusions: EVs from MSCs reduce neuroinflammation in hippocampus and cerebellum and restore cognitive and motor function in hyperammonemic rats. EVs from MSCs may be useful to improve cognitive function in patients with MHE.

12:30 – 13:00 Susana Torres

Role of Galectin-3 as an immunosuppressive regulator in 3D models in non-small cell lung cancer (NSCLC). Translational implications.

As the leading cause of cancer death worldwide, lung cancer remains a major burden on healthcare systems and cause significant challenges for clinicians and patients, with ~15% of patients surviving five years after diagnosis. In recent years, there has been an increasing recognition of the immune system’s role in cancer development and progression, focusing on using immunotherapy in the clinic. The role of the immune system during tumorigenesis is crucial. There is a lot of evidence indicating that tumour cells can create an immunosuppressive microenvironment that favours tumour development and spreading. Due to the fact that interactions between tumour cells and immune cells are involved in the down-regulation of the immune response allowing tumour escape from immunosurveillance, a better understanding of how tumour cells interact with their immune microenvironment in NSCLC will result in an improved characterization of patient`s immune contexture (through the use of biomarkers), and new immunotherapeutic protocols which may overcome the limitations of conventional therapeutic strategies. This study explores the role of Galectin-3, an immunoregulatory factor, in the lung cancer microenvironment using tumorspheres (3D models) and evaluates its predictive and prognostic impact in adenocarcinoma (ADC) NSCLC patients. We revealed that Galectin-3 represents a potential factor that modulates the immune microenvironment by regulating Tregs and might be used as a prognostic factor for improved survival in early ADC NSCLC patients and can also be used as a predictive and prognostic factor for improved survival in advanced ADC NSCLC patients treated with first-line pembrolizumab.