Neuropsychiatric Disorders in Dementia: Mechanisms of Development and Approaches to Correction

Neuroscience and Behavioral Physiology - Dementia is often combined with other mental disorders which can manifest at different stages of the disease. The severity and rate of progression of these...     

Effects of the Interaction of the ANKK1/DRD2 TaqIA and HTR2C Cys23Ser Polymorphisms on Approach Motivation in Schizophrenia Patients and Healthy People

Neuroscience and Behavioral Physiology - Objective. To assess the association of the DRD2 gene and its interaction with the HTR2C gene with the characteristics of the hedonistic and activatory...     

Efficacy of Music Therapy in the Rehabilitation of Stroke Patients

Neuroscience and Behavioral Physiology - Objective. To assess the dynamics of recovery of motor, speech, and autonomous functions in patients with ischemic stroke (IS) using music therapy....     

Use of Anchoring Motifs to Support the Central and Peripheral Locations of Opsins in Optogenetics

Neuroscience and Behavioral Physiology - One version of the optogenetic prosthetization of the degenerative retina is an approach based on creation of an ON/OFF receptive field for ganglion neurons...     

Comparative Characteristics of the Expression of Inducible NO Synthase in the Hippocampus of Humans and Experimental Animals

Neuroscience and Behavioral Physiology - Objective: To study the characteristics of the expression of inducible NO synthase (iNOS) in hippocampal fields CA1 and CA3 in adult male humans and adult...     

Multi-cellularity in cardiac tissue engineering,how close are we to native heart tissue?

Journal of Muscle Research and Cell Motility - Tissue engineering is a complex field where the elements of biology and engineering are combined in an attempt to recapitulate the native environment...     

Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.