7 research outputs found
Tumor derived Microvesicles enhance cross-processing ability of clinical grade Dendritic Cells
Tumor cells release extracellular microvesicles (MVs) in the microenvironment to deliver biological signals to neighbouring cells as well as to cells in distant tissues.
Tumor-derived MVs appear to play contradictory role promoting both immunosuppression and tumor growth and both evoking tumor specific immune response. Recent evidences indicate that tumor-derived MVs can positively impact Dendritic Cells (DCs) immunogenicity by reprogramming DC antigen processing machinery and intracellular signaling pathways, thus promoting anti-tumor response.
DCs are considered pivot cells of the immune system due to their exclusive ability to coordinate the innate and acquired immune responses, cross-present exogenous antigens and prime naïve T cells. DCs are required for the induction and maintenance of long-lasting anti-tumor immunity and their exploitation has been extensively investigated for the design of anti-tumor vaccines. However, the clinical grade culture conditions that are required to generate DCs for therapeutic use can strongly affect their functions.
Here, we investigated the immunomodulatory impact of MVs carrying the MUC1 tumor glycoantigen (MVsMUC1) as immunogen formulation on clinical grade DCs grown in X-VIVO 15 (X-DCs). Results indicated that X-DCs displayed reduced performance of the antigen processing machinery in term of diminished phagocytosis and acidification of the phagosomal compartment suggesting an altered immunogenicity of clinical grade DCs. Pulsing DCs with MVsMUC1 restored phagosomal alkalinization, triggering ROS increase. This was not observed when a soluble MUC1 protein was employed (rMUC1). Concurrently, MVsMUC1 internalization by X-DCs allowed MUC1 cross-processing. Most importantly, MVsMUC1 pulsed DCs activated IFNγ response mediated by MUC1 specific CD8+ T cells. These results strongly support the employment of tumor-derived MVs as immunogen platforms for the implementation of DC-based vaccine
Tsallis non-extensive statistics, intermittent turbulence, SOC and chaos in the solar plasma. Part one: Sunspot dynamics
In this study, the nonlinear analysis of the sunspot index is embedded in the
non-extensive statistical theory of Tsallis. The triplet of Tsallis, as well as
the correlation dimension and the Lyapunov exponent spectrum were estimated for
the SVD components of the sunspot index timeseries. Also the multifractal
scaling exponent spectrum, the generalized Renyi dimension spectrum and the
spectrum of the structure function exponents were estimated experimentally and
theoretically by using the entropy principle included in Tsallis non extensive
statistical theory, following Arimitsu and Arimitsu. Our analysis showed
clearly the following: a) a phase transition process in the solar dynamics from
high dimensional non Gaussian SOC state to a low dimensional non Gaussian
chaotic state, b) strong intermittent solar turbulence and anomalous
(multifractal) diffusion solar process, which is strengthened as the solar
dynamics makes phase transition to low dimensional chaos in accordance to
Ruzmaikin, Zeleny and Milovanov studies c) faithful agreement of Tsallis non
equilibrium statistical theory with the experimental estimations of i)
non-Gaussian probability distribution function, ii) multifractal scaling
exponent spectrum and generalized Renyi dimension spectrum, iii) exponent
spectrum of the structure functions estimated for the sunspot index and its
underlying non equilibrium solar dynamics.Comment: 40 pages, 11 figure
Tumor-Derived Microvesicles Enhance Cross-Processing Ability of Clinical Grade Dendritic Cells
Tumor cells release extracellular microvesicles (MVs) in the microenvironment to deliver biological signals to neighboring cells as well as to cells in distant tissues. Tumor-derived MVs appear to play contradictory role promoting both immunosuppression and tumor growth and both evoking tumor specific immune response. Recent evidences indicate that tumor-derived MVs can positively impact Dendritic Cells (DCs) immunogenicity by reprogramming DC antigen processing machinery and intracellular signaling pathways, thus promoting anti-tumor response. DCs are considered pivot cells of the immune system due to their exclusive ability to coordinate the innate and acquired immune responses, cross-present exogenous antigens, and prime naïve T cells. DCs are required for the induction and maintenance of long-lasting anti-tumor immunity and their exploitation has been extensively investigated for the design of anti-tumor vaccines. However, the clinical grade culture conditions that are required to generate DCs for therapeutic use can strongly affect their functions. Here, we investigated the immunomodulatory impact of MVs carrying the MUC1 tumor glycoantigen (MVsMUC1) as immunogen formulation on clinical grade DCs grown in X-VIVO 15 (X-DCs). Results indicated that X-DCs displayed reduced performance of the antigen processing machinery in term of diminished phagocytosis and acidification of the phagosomal compartment suggesting an altered immunogenicity of clinical grade DCs. Pulsing DCs with MVsMUC1 restored phagosomal alkalinization, triggering ROS increase. This was not observed when a soluble MUC1 protein was employed (rMUC1). Concurrently, MVsMUC1 internalization by X-DCs allowed MUC1 cross-processing. Most importantly, MVsMUC1 pulsed DCs activated IFNγ response mediated by MUC1 specific CD8+ T cells. These results strongly support the employment of tumor-derived MVs as immunogen platforms for the implementation of DC-based vaccines