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Jennifer L. Schehr
P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
P3.04-08 - Identifying Resistance to Immune Checkpoint Inhibitors by Screening for PD-L1 and MHC I Expression on CTCs in Pts with NSCLC (ID 14173)
12:00 - 13:30 | Author(s): Jennifer L. Schehr
PD-L1 expression on tumor predicts benefit to immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC. However, there are a significant number of patients whose tumor test positive for PD-L1 expression that do not derive benefit from ICIs, suggesting the existence of intrinsic resistance mechanisms. PD-L1 blockade aims to trigger tumor cell recognition and lysis by CD8+ T cells, but this process requires concordant expression of MHC I by tumor cells. Recently, MHC I negativity was observed in 49% of patients with lung carcinoma, and correlated with a lack of CD8+ T cell infiltration, emphasizing the importance of screening for MHC I in combination with PD-L1.a9ded1e5ce5d75814730bb4caaf49419 Method
For the purposes of both screening and the detection of acquired resistance, we developed a minimally invasive diagnostic test using Circulating Tumor Cells (CTCs). CTCs were captured and stained on the ExtractMax system (Gilson, Inc.) with Exclusion-Based Sample Processing (ESP) technology (Salus Discovery, LLC). With automation, the ExtractMax simplifies complex multi-step procedures, reduces variability, and ensures gentle manipulation of rare cell targets for optimal yield and viability.4c3880bb027f159e801041b1021e88e8 Result
A range of PD-L1 and MHC I expression levels were detected on CTCs captured from a cohort of patients with NSCLC, with two patients showing no MHC 1 expression and all others with heterogeneous expression of MHC 1. PD-L1 expression was variable across all samples tested with subset of patients with PD-L1 positive CTCs but MHC I negative, suggesting intrinsic resistance to PD-L1 targeted therapies.
This data supports the feasibility of using an automated CTC processing system to detect and monitor PD-L1 and MHC I expression in patients with NSCLC. Ongoing efforts include expanding this patient cohort in larger clinical trials and transitioning this test into a clinical laboratory testing facility for regulatory approval and use as a clinically actionable diagnostic tool.6f8b794f3246b0c1e1780bb4d4d5dc53
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