Immunotherapy reverses glioma-driven dysfunction of immune system homeostasis

• DOI: 10.1136/jitc-2022-004805
• Publication Date: 2023-02-07T16:57:08Z
• Authors: Bayli DiVita Dean; Tyler Wildes; Joseph Dean; Oleg Yegorov; Changlin Yang; David Shin; Connor Francis; John W Figg; Mathew Sebastian; Laura Falceto Font; Dan Jin; Alexandra Reid; Ginger Moore; Brandon Fernandez; Brandon Wummer; Carmelle Kuizon; Duane Mitchell; Catherine T Flores
• Keywords: Myeloid-derived Suppressor Cell

Background Glioma-induced immune dysregulation of the hematopoietic system has been described in a limited number studies. In this study, our group further demonstrates that gliomas interrupt cellular differentiation programming and outcomes stem progenitor cells (HSPCs) bone marrow. HSPCs from glioma-bearing mice are reprogrammed driven towards expansion myeloid lineage precursors myeloid-derived suppressor (MDSCs) secondary lymphoid organs. However, we found is reversed by immunotherapy. Adoptive therapy (ACT) demonstrably efficacious multiple preclinical models central nervous (CNS) malignancies, here describe how glioma-induced dysfunction immunotherapeutic platform. Methods The impact orthotopic KR158B-luc glioma on was evaluated an unbiased fashion using single cell RNAseq (scRNAseq) − phenotypically flow cytometry. Mature frequencies function were also Finally, ACT containing total body irradiation, tumor RNA-pulsed dendritic cells, tumor-reactive T isolated or non-tumor-bearing used to evaluate fate survival. Results Using scRNAseq, observed altered HSPC landscape versus . addition, subsets, including granulocyte macrophage (GMPs) MDSCs, relative controls. Furthermore, MDSCs demonstrated increased suppressive capacity toward tumor-specific as compared with hosts. Interestingly, treatment overcame these properties. When transferred context ACT, significant survival benefit long-term cures treated non-glioma-bearing HSPCs.