In order to examine the mechanisms by which clonal deletion of autoreactive T cells occurs, a peptide antigen was used to induce deletion of antigen-reactive thymocytes in vivo. Mice transgenic for a ...T cell receptor (TCR) that reacts to this peptide contain thymocytes that progress from the immature to the mature phenotype. Intraperitoneal administration of the peptide antigen to transgenic mice results in a rapid deletion of the immature CD4
+
CD8
+
TCR
lo
thymocytes. Apoptosis of cortical thymocytes can be seen within 20 hours of treatment. These results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance.
High-grade gliomas are notoriously heterogeneous regarding antigen expression, effector responses, and immunosuppressive mechanisms. Therefore, combinational immune therapeutic approaches are more ...likely to impact a greater number of patients and result in longer, durable responses. We have previously demonstrated the monotherapeutic effects of miR-124, which inhibits the signal transducer and activator of transcription 3 (STAT3) immune suppressive pathway, and immune stimulatory 4-1BB aptamers against a variety of malignancies, including genetically engineered immune competent high-grade gliomas. To evaluate potential synergy, we tested an immune stimulatory aptamer together with microRNA-124 (miRNA-124), which blocks tumor-mediated immune suppression, and found survival to be markedly enhanced, including beyond that produced by monotherapy. The synergistic activity appeared to be not only secondary to enhanced CD3
+
cell numbers but also to reduced macrophage immune tumor trafficking, indicating that a greater therapeutic benefit can be achieved with approaches that both induce immune activation and inhibit tumor-mediated immune suppression within the central nervous system (CNS) tumors.
Results of a study suggest that early regulation of interleukin-4 and interleukin-10 in a developing immune response and the identity of the initiating antigen-presenting cells are critical in ...determining the Th phenotype of the developing T cells.
The overall objective of this chapter is to evaluate significant progress and research advances within the field of immunotherapy and to delineate the challenges associated with the utilization of ...immunotherapies that are unique to central nervous system (CNS) tumors. Immunotherapy of CNS tumors is complicated by multiple factors, such as, tumor heterogeneity, immunosuppression, and immunologic privilege. The study of immunotherapies requires a thorough knowledge of immunological response within the CNS and its potential consequences, including the induction of autoimmune disorders, is mandatory.
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