Biology subjects

Camacho-Toledano, C.

Publications and source records attributed to Camacho-Toledano, C..

3 recordsLinked to original sources

bioRxiv2023

GRAPHENE OXIDE AS A NOVEL IMMUNOTHERAPY TOOL FOR THE MODULATION OF MYELOID-DERIVED SUPPRESSOR CELL ACTIVITY IN THE CONTEXT OF MULTIPLE SCLEROSIS

Multiple Sclerosis (MS) is a chronic, inflammatory disease of the central nervous system. Despite the pharmacological arsenal approved for MS, there are treatment-reluctant patients for whom cell therapy appears as the only therapeutic alternative. Myeloid-derived suppressor cells (MDSCs) are immature cells of the innate immune response able to immunosuppress T lymphocytes and to promote oligodendroglial differentiation in experimental autoimmune encephalomyelitis (EAE), a preclinical model for MS. Culture devices need to be designed so that MDSCs maintain a state of immaturity and immunosuppressive function similar to that exerted in the donor organism. Graphene oxide (GO) has been described as a biocompatible material with the capacity to biologically modulate different cell types, including immune cells. In the present work, we show how MDSCs isolated from immune organs of EAE mice maintain an immature phenotype and highly immunosuppressive activity on T lymphocytes after being cultured on 2D reduced GO films (rGO200) compared to those grown on glass. This activity is depleted when MDSCs are exposed to slightly rougher and more oxidized GO substrates (rGO90). The greater reduction in cell size of cells exposed to rGO90 compared to rGO200 is associated with the activation of apoptosis processes. Taken together, the exposure of MDSCs to GO substrates with different redox state and roughness appears as a good strategy to control MDSC activity in vitro. This versatility of GO nanomaterials and the impact of their physico-chemical properties in immunomodulation open the door to its possible selective therapeutic use for pathologies where MDSCs need to be enhanced or inhibited.

immunology↗

bioRxiv2022

Peripheral Myeloid-Derived Suppressor Cells are good biomarkers of the efficacy of Fingolimod in Multiple Sclerosis

The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition of inhibiting T cell egression from lymph nodes, fingolimod promotes the immunosuppressive activity of Myeloid-Derived Suppressor Cells (MDSCs), a cell type that can be used as a biomarker of disease severity, and of the degree of demyelination and extent of axonal damage in MS. In the present study, we have assessed whether the abundance of circulating monocytic-MDSCs (M-MDSCs) may represent a useful biomarker of fingolimod efficacy. As such, blood immune cells were analyzed at disease onset in the experimental autoimmune encephalomyelitis (EAE) MS mouse model. Fingolimod treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. The data obtained indicated that the M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e. patients who met at least two of the criteria used to define non-evidence of disease activity (NEDA-3) 12 months after treatment, providing relevant information of intention-to-treat MS patients. Collectively, our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod.

immunology↗

bioRxiv2022

Myeloid-Derived Suppressor Cells are relevant factors to predict the severity of multiple sclerosis

Multiple Sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Previous retrospective investigations in the MS model, experimental autoimmune encephalomyelitis (EAE), highlighted the important relationship between monocytic-myeloid-derived suppressor cells (M-MDSCs) and the experimented severity of the clinical course. In this work, we show for the first time cells resembling M-MDSCs associated to MS lesions, whose abundance was related to milder MS clinical courses. Moreover, Ly-6Chi cells (which are indistinguishable from circulating M-MDSCs in mice) are useful biomarkers to predict a milder severity of the EAE disease course and a lesser tissue damage extent. Finally, the abundance of M-MDSCs in blood from untreated MS patients at their first relapse was inversely correlated with EDSS at baseline and relapse recovery one-year later. In summary, our data point to M-MDSC load as a promising biomarker of patients clinical course severity. TeaserThe abundance of myeloid-derived suppressor cells is related to a milder clinical course in multiple sclerosis patients.

neuroscience↗