Im-10 * Effects of T-cell Tgf- Signaling Abrogation on Survival in Pediatric Glioma
Year: 2015
Type: conference-abstract
Abstract: We have been investigating the effects of immune system modulation on brain tumor survival in animal models of pediatric malignancies. For example, TGF-β is produced by various tumor types and dampens the response of the immune system, preventing recognition of tumor cells. Thus, we crossed mice with T-cell-specific TGF-β blockade (CD4-TGFβRII-DNR) with a mouse model of medulloblastoma (SmoA1 transgenic mice) and analyzed offspring. We noted dramatic infiltration of T cells into the tumor and coincident improvement in survival of these mice. Furthermore, there was a striking change in T cell phenotype—notably a large increase in memory T cells in double transgenic mice, which are in principle able to mount anti-tumor immunity. We've been employing a novel piggyBac model of forebrain glioma to rapidly generate tumors from patient driver genes. Interestingly, using genome-wide analysis, many members of the TGF-β ligand family are upregulated by tumor cells and these secreted ligands appear to be the principle immunosuppressive molecules expressed by the tumor propagating population. Given the survival-promoting role of T cell TGF-β signaling blockade in our medulloblastoma model, we have generated de novo tumors in CD4-TGFβRII-DNR mice using our in vivo piggyBac system and are investigating the applicability of this strategy in pediatric forebrain glioma.
Source: Neuro-Oncology
Authors: J. Breunig, M. Danielpour, R. Levy, M. Dutra-Clarke
Institution: Cedars-Sinai Medical Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1995264785