For medulloblastoma patients, the current therapeutic paradigm of surgery followed by radiation and chemotherapy can lead to long-term remission. However, the sequelae of treatment can be very debilitating, particularly in young children. Immunotherapy is an attractive treatment approach to optimize the targeting of tumor cells while sparing the vulnerable surrounding brain that is still developing in children. Understanding the relationship between medulloblastoma and the immune system is critical to develop effective immunologic-based treatment strategies for these patients. This review focuses on current knowledge of tumor immunology and the factors that contribute to the lack of immune system recognition of these tumors. The specificity of tumor antigens present in medulloblastoma is also discussed along with a summary of early clinical immunotherapy results.
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http://dx.doi.org/10.1007/s11060-011-0776-1 | DOI Listing |
Mol Neurodegener
January 2025
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.
View Article and Find Full Text PDFNat Med
January 2025
Department of Neurology & Neurological Sciences, Stanford Movement Disorders Center, Stanford University, Stanford, CA, USA.
Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms.
View Article and Find Full Text PDFSci Rep
January 2025
Medical Genome Center, Research Institute, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, 474-8511, Aichi, Japan.
The prevalence of Alzheimer's disease (AD) is increasing as society ages. The details of AD pathogenesis have not been fully elucidated, and a comprehensive gene expression analysis of the process leading up to the onset of AD would be helpful for understanding the mechanism. We performed an RNA sequencing analysis on a cohort of 1227 Japanese blood samples, representing 424 AD patients, 543 individuals with mild cognitive impairment (MCI), and 260 cognitively normal (CN) individuals.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Oncolytic viruses (OVs) emerge as a promising cancer immunotherapy. However, the temporal impact on tumor cells and the tumor microenvironment, and the nature of anti-tumor immunity post-therapy remain largely unclear. Here we report that CD4 T cells are required for durable tumor control in syngeneic murine models of glioblastoma multiforme after treatment with an oncolytic herpes simplex virus (oHSV) engineered to express IL-12.
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