IMMU-21. GLIOMA-DERIVED FACTORS RECRUIT AND INDUCE AN IMMUNE SUPPRESSIVE PHENOTYPE IN BONE MARROW-DERIVED CCR2+ MYELOID CELLS

نویسندگان

چکیده

Abstract INTRODUCTION Infiltrating immune-suppressive myeloid cells represent a tumor supportive population that contributes to immune checkpoint inhibitor resistance and poor survival in Glioblastoma (GBM) patients. We have previously characterized monocytic-myeloid derived suppressor (M-MDSCs) based on their dual expression of chemokine receptors CCR2 CX3CR1(CCR2+/CX3CR1+). Genetic pharmacologic targeting CCR2, combination with PD-1 blockade, reduced the percentage M-MDSCs glioma-microenvironment slowed progression KR158 005GSC murine gliomas. Additional studies are needed investigate chemokines responsible for recruitment CCR2+/CX3CR1+ impact glioma factors suppressive phenotype. OBJECTIVE Evaluate effect migration suppression bone marrow cells. METHODS A transwell assay was utilized determine migratory ability KR158B conditioned presence CCL2 CCL7 neutralizing antibodies. Ly6G-/GR1+ were isolated from cultured media co-cultured freshly T-cells examine RESULTS gliomas differentially upregulate cytokines including CCL2, IL6, G-CSF, GM-CSF as compared healthy naive brains. increased marrow-derived CD11b+, Ly6Chi, Ly6G-. Bone expanded condition suppress both CD4+ CD8+ T cell proliferation. migrate recombinant well media. Migration is completely inhibited by High associated prognosis human GBM. CONCLUSION Glioma-derived mediate CCR2+ into microenvironment redundant manner. glioma-derived induce CD4/8+ state.

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ژورنال

عنوان ژورنال: Neuro-oncology

سال: 2022

ISSN: ['1523-5866', '1522-8517']

DOI: https://doi.org/10.1093/neuonc/noac209.519