Imps-25differential Tumor Microenvironments and Response to Immune Checkpoint Blockade in Molecular Subtypes of Murine Medulloblastoma
Year: 2015
Type: article
Abstract: PURPOSE: Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma (MB), the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and Group 3 MB for preclinical evaluation in immunocompetent C57BL/6 mice. METHODS AND RESULTS: Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid derived suppressor cells and tumor-associated macrophages in murine SHH model tumors compared with Group 3 tumors. However, murine Group 3 tumors had higher percentages of CD8+ PD-1+ T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial Group 3 tumors compared to SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. CONCLUSIONS: This is the first immunologic characterization of preclinical models of molecular subtypes of MB, and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings provide strong evidence for distinct immunophenotypes across subtypes of MB that have important value in the clinical application of relevant immunotherapeutic strategies targeting MB.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2585710743