INNV-10. PERIPHERAL MYELOID CELL pd-l1 IS A BIOMARKER FOR HIGH-GRADE INTRACRANIAL MALIGNANCY
Year: 2018
Type: conference-abstract
Abstract: Immunosuppression is a hallmark feature of primary and metastatic malignancies in the brain. Expansion of suppressive myeloid cells expressing PD-L1 has been demonstrated in circulation of GBM patients. Similar findings have been reported in numerous advanced malignancies, but the presence of suppressive myeloid cells is rarely seen in patients with benign tumors. We hypothesized that expression of PD-L1 on peripheral myeloid cells may be used to differentiate malignant from non-malignant brain tumors prior to tissue diagnosis. Peripheral blood was collected from 189 patients undergoing surgical resection of tumors, including low grade gliomas (n=5), high grade gliomas/GBM (n=76), benign meningiomas (n=18), atypical meningiomas (n=25), anaplastic meningiomas (n=10), non-metastatic early stage NSCLC (n=15), and brain-metastatic NSCLC (n=34), as well as from healthy donors (n=6). Immunosuppressive myeloid cells (CD45+CD11b+CD163+/-PD-L1+) and myeloid-derived suppressor cells (MDSCs) (CD11b+CD33+HLA-DRloPD-L1+/-) were quantified through flow cytometry. Peripheral myeloid PD-L1 positivity was significantly elevated in patients with high grade vs. low grade gliomas (19.7% vs. 5.7%; p<0.0001), anaplastic vs. other meningiomas (12.6% vs. 6.2%; p<0.01), and brain-metastatic vs. non-metastatic NSCLC (11.3% vs. 4.1%; p<0.0001). Using a threshold of 10%, peripheral monocyte PD-L1 expression was found to be predictive of high grade malignancy with a positive predictive value of 95.2%. Sensitivity was 57.1% and specificity was 96.2%. MDSC abundance was also significantly increased in patients with high grade tumors (36.3% in gliomas, 14.4% in meningiomas, 18.0% in metastatic NSCLC) compared to lower grade tumors (11.4%) and healthy donors (5.7%). Expansion of PD-L1+ myeloid cells is strongly associated with the presence of intracranial malignancy, with a predictive value in excess of 95% for patients with an intracranial mass. In cases where pre-biopsy knowledge of a high-grade malignancy may change the surgical approach to diagnosis and treatment, blood analysis for myeloid PD-L1 may be considered as a first step.
Source: Neuro-Oncology
Authors: Yuping Li, Jonathan Lamano, Joseph DiDomenico, Dauren Biyashev, Dorina Veliceasa, Gurvinder Kaur, Jason Lamano, Orin Bloch
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2899630164