EXTH-70. IMMUNOTHERAPY REVERSES GLIOMA-DRIVEN DYSFUNCTION OF IMMUNE SYSTEM HOMEOSTASIS
نویسندگان
چکیده
Abstract BACKGROUND Glioma-induced immune disfunction has been described in a limited number of studies, and here we further demonstrate that gliomas also interrupt the cellular differentiation programming outcomes hematopoietic stem cells (HSC) bone marrow. HSCs from glioma-bearing mice are re-programmed driven towards expansion myeloid lineage precursors myeloid-derived suppressor (MDSC) secondary lymphoid organs. However, found this is reversed by immunotherapy. Adoptive therapy (ACT) demonstrably efficacious multiple preclinical models CNS malignancies, describe how glioma-induced immunotherapeutic platform. METHODS The impact orthotopic KR158B glioma on was evaluated an unbiased fashion using single cell RNAseq lineage- phenotypically flow cytometry. Mature frequencies function were Finally, ACT containing total body irradiation, tumor-specific dendritic cells, tumor-reactive T isolated or non-tumor-bearing used to evaluate fate survival. RESULTS We observed differential gene expression tumor-bearing versus healthy coupled with subsets mice. Interestingly, MDSCs demonstrated hyper suppressive capacity as compared hosts. treatment overcame properties HSCs. When transferred ACT, significant survival benefit long-term cures treated non-glioma-bearing HSPCs. CONCLUSIONS These findings disposition hosts can be redirected for benefit. Collectively, these data compartment at progenitor level promote their progenitors. overcome bias provide lasting anti-tumor effects.
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ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac209.868