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James Lindsay



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-27 - Clinical Implementation of Multiplex Immunofluorescence to Characterize Tumor Immune Status in Lung Cancer Patients (Now Available) (ID 2925)

      10:15 - 18:15  |  Author(s): James Lindsay

      • Abstract
      • Slides

      Background

      Tumor cell PD-L1 positivity by immunohistochemistry (IHC) enriches for response with PD-(L)1 inhibitors in patients with non-small cell lung carcinoma (NSCLC). However, PD-L1 IHC has limited positive and negative predictive value and does not provide information about the immune effector cell population in the tumor environment. Multiplex immunofluorescence (MIF) can be used to simultaneously characterize checkpoint proteins and immune cell infiltrates on a single tumor slide. MIF is not, however, routinely used in clinical practice. We operationalized and launched prospective MIF for lung cancer patients.

      Method

      Patients were consented to an institutional protocol for tumor sequencing and immunoprofiling. Samples were submitted for MIF reflexively following a diagnosis of lung cancer on any in-house core biopsy or resection specimen. Slides were reviewed by a pathologist and imaging scientist to confirm tumor adequacy and three to six representative 20X fields of view that included tumor and tumor-stroma interface were selected for scoring. Automated staining for AE1/AE3, PD-L1, PD-1, CD8, FoxP3 and DAPI was carried out on a Leica BOND RX Autostainer and imaged using the Polaris imaging system (PerkinElmer). Under pathologist supervision, biomarkers were quantified in each region at a single cell level using the Inform Advanced Image Analysis Software (PerkinElmer). An automated reporting system calculated a PD-L1 tumor proportion score (TPS) and immune cell density across the analyzed regions.

      Result

      To date, 80 samples have been received for analysis (40% biopsies and 60% resections), of which 78 (98%) were imaged successfully. Average turnaround time from receipt of specimen to complete reporting was 25 days. PD-L1 was considered positive (TPS >50%) in 4 (5%), low positive (1-49%) in 42 (55%), and negative (<1%) in 32 (41%). CD8+/PD1+ density ranged from 0 to >800/mm2 (median 59) and FOXP3+ cells from 2 to >700/mm2 (median 59); both showed a broad standard deviation, consistent with heterogeneity in the tumor and adjacent stroma. Nine (11%) tumors showed a pattern of adaptive immune resistance (so-called “hot” tumors), defined as CD8+/PD1+ density greater than the median and at least low positive PD-L1 TPS.

      Conclusion

      Multiplex immunofluorescence and pathologist-guided image analysis of fixed tissue specimens can be integrated into clinical practice with a low rate of failure and acceptable turn-around time to identify unique immunologic subsets of lung cancer. Limitations of data storage and analysis speed require focused field selection, therefore optimization of the scored area(s) is essential to ensure accurate tumor immune classification. Studies to determine the feasibility of use of MIF for selection of patients for immunotherapy are ongoing.

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