Showing papers by "Sandra O. Gollnick published in 2010"
TL;DR: It is demonstrated that incubation of Prx1 with thioglycollate-elicited murine macrophages or immature bone marrow-derived dendritic cells resulted in TLR4-dependent secretion of TNF-α and IL-6 and dendrite cell maturation, suggesting that Prx 1 may act as danger signal similar to other TLR 4-binding chaperone molecules such as HSP72.
Abstract: Peroxiredoxin 1 (Prx1) is an antioxidant and molecular chaperone that can be secreted from tumor cells. Prx1 is overexpressed in many cancers, and elevation of Prx1 is associated with poor clinical outcome. In the current study, we demonstrate that incubation of Prx1 with thioglycollate-elicited murine macrophages or immature bone marrow-derived dendritic cells resulted in TLR4-dependent secretion of TNF-α and IL-6 and dendritic cell maturation. Optimal secretion of cytokines in response to Prx1 was dependent upon serum and required CD14 and MD2. Binding of Prx1 to thioglycollate macrophages occurred within minutes and resulted in TLR4 endocytosis. Prx1 interaction with TLR4 was independent of its peroxidase activity and appeared to be dependent on its chaperone activity and ability to form decamers. Cytokine expression occurred via the TLR-MyD88 signaling pathway, which resulted in nuclear translocation and activation of NF-κB. These findings suggest that Prx1 may act as danger signal similar to other TLR4-binding chaperone molecules such as HSP72.
184 citations
TL;DR: The current state of investigations into the ability of PDT to enhance anti-tumor immunity, the mechanisms behind this enhancement and the future of PDT as an immunotherapy are addressed in this review.
Abstract: Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumors, resulting in cure of early disease and palliation of advanced disease. PDT was originally considered to be a local treatment; however, both pre-clinical and clinical studies have shown that local PDT treatment of tumors can enhance systemic anti-tumor immunity. The current state of investigations into the ability of PDT to enhance anti-tumor immunity, the mechanisms behind this enhancement and the future of PDT as an immunotherapy are addressed in this review.
138 citations
TL;DR: The importance of different accessory proteins in antigen presentation, including the heterodimeric transporter associated with antigen processing, TAP and tapasin, are reviewed and the progress in understanding of alternate splicing in antigenPresentation is reviewed.
Abstract: The expression of major histocompatibility complex (MHC) class I molecules on the cell surface is critical for recognition by cytotoxic T lymphocytes (CTL). This recognition event leads to destruction of cells displaying MHC class I—viral peptide complexes or cells displaying MHC class I—mutant peptide complexes. Before they can be transported to the cell surface, MHC class I molecules must associate with their peptide ligand in the endoplasmic reticulum (ER) of the cell. Within the ER, numerous proteins assist in the appropriate assembly and folding of MHC class I molecules. These include the heterodimeric transporter associated with antigen processing (TAP1 and TAP2), the heterodimeric chaperone-oxidoreductase complex of tapasin and ERp57 and the general ER chaperones calreticulin and calnexin. Each of these accessory proteins has a well-defined role in antigen presentation by MHC class I molecules. However, alternate splice forms of MHC class I heavy chains, TAP and tapasin, have been reported suggesting additional complexity to the picture of antigen presentation. Here, we review the importance of these different accessory proteins and the progress in our understanding of alternate splicing in antigen presentation.
29 citations
TL;DR: It is suggested that tumor cells may contain alternate splice forms of tapasin which may regulate MHC class I antigen presentation, which is known to regulate many genes in the context of mutations.
18 citations
Patent•
08 Dec 2010
TL;DR: In this article, compositions and methods for stimulating immune responses against antigens are provided, where the compositions contain an antigen to which a stimulated immune response is desired and an isolated protein that functions as an adjuvant.
Abstract: Provided are compositions and methods for stimulating immune responses against antigens The compositions contain an antigen to which a stimulated immune response is desired and an isolated Prx 1 protein The Prx 1 protein functions as an adjuvant so that the immune response to the antigen stimulated by the composition comprising the antigen and Prx 1 is greater than the immune response stimulated by the antigen alone
1 citations
Patent•
08 Dec 2010
TL;DR: In this article, a method for inhibiting angiogenesis in a tumor was proposed, which involves administering to an individual who has a tumor a composition that contains an agent capable of inhibiting binding of peroxiredoxin 1 (Prx1) to Toll-like receptor 4 (TLR4) such that angogenesis in the tumor is inhibited subsequent to the administration.
Abstract: Provided is a method for inhibiting angiogenesis in a tumor. The method involves administering to an individual who has a tumor a composition that contains an agent capable of inhibiting binding of peroxiredoxin 1 (Prx1) to Toll like receptor 4 (TLR4) such that angiogenesis in the tumor is inhibited subsequent to the administration. The agent that is capable of inhibiting binding of Prx1 to TLR4 can be an antibody to Prx1, a Prx1 binding fragment of the antibody, or a peptide. The peptide can be capable of inhibiting the formation of a Prx1 decamer, or can inhibit binding of Prx1 to TLR4 by steric interference, or by competitions with Prx1 for TLR4 binding. The tumor in which angiognesis is inhibited can be any type of cancer tumor.
1 citations