111 Integrating multidimensional mass cytometry and multiplex immunohistochemistry to infer spatial relationships between human glioblastoma infiltrating immune cells that correlate with patient outcome

BackgroundGlioblastomas (GBM) account for ~60% of adult primary brain tumors. With few advances in therapeutics, median overall survival remains 15-months post-diagnosis. Immunotherapies may provide therapeutic benefit; however, no predictive immune features have informed therapeutic stratification....

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Published in:Journal for immunotherapy of cancer 2022-11, Vol.10 (Suppl 2), p.A121-A121
Main Authors: Bartkowiak, Todd, Brockman, Asa, Lima, Sierra, Hayes, Madeline, Roe, Caroline, Sinnaeve, Justine, Mistry, Akshitkumar, Leelatian, Nalin, Mobley, Bret, Chambless, Lola, Thompson, Reid, Weaver, Kyle, Ihrie, Rebecca, Irish, Jonathan
Format: Article
Language:English
Subjects:
Biomarkers
Brain cancer
Consent
Immunotherapy
Lymphocytes
Medical prognosis
Metabolism
Patients
Review boards
Tumors
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Summary:BackgroundGlioblastomas (GBM) account for ~60% of adult primary brain tumors. With few advances in therapeutics, median overall survival remains 15-months post-diagnosis. Immunotherapies may provide therapeutic benefit; however, no predictive immune features have informed therapeutic stratification. Radiographic tumor contact with the lateral ventricle (C-GBM) correlates with 7-months worse prognosis compared to patients with ventricle non-contacting GBM (NC-GBM), yet the influence of ventricle contact on anti-tumor immunity is unknown. This study characterized the GBM immune microenvironment and identified targetable mechanisms of immunosuppression correlating with worse outcomes in C-GBM patients.MethodsPrimary glioblastoma tissue was provided with written informed consent in accordance with the Declaration of Helsinki and with approval of the Vanderbilt Institutional Review Board (IRB #131870). Seventeen patients presented with primary, IDH-wildtype C-GBM and 15 with NC-GBM. Machine learning integrated 1) mass cytometry immunophenotyping, 2) metabolic phenotypes, 3) immune cytokine response patterns and induced intracellular signaling networks, and 4) matched multiplex immunohistochemistry on FFPE embedded tissue to identify phenotypic, functional, and spatial biomarkers correlating with patient outcome.ResultsC-GBM tumors were enriched in STAT3-driven CD32+CD44+HLA-DR+ monocyte-derived macrophages (MDM) compared to NC-GBM (19 ± 8% vs. 6 ± 2%; p
ISSN:2051-1426
DOI:10.1136/jitc-2022-SITC2022.0111