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Geoffrey Peters



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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-039 - Spatial Heterogeneity of Immunological Markers Between Cores and Complete NSCLC Sections Using Multispectral Fluorescent IHC (ID 9728)

      09:30 - 16:00  |  Presenting Author(s): Geoffrey Peters

      • Abstract
      • Slides

      Background:
      Immunotherapy with immune checkpoint inhibitors have revolutionised the management of solid organ malignancy including melanoma and NSCLC. Direction has turned to the tumour immune microenvironment (TIM) to explore predictive biomarkers. The spatial arrangement of immune infiltrative cells has the potential to better explain the TIM. Vectra multispectral immunohistochemistry (IHC) allows accurate definition of the TIM and may help detect mechanisms of immune evasion.

      Method:
      Multispectral fluorescent immunohistochemistry with a panel including CKAE1/3, CD8, FOXP3 and PD-L1 (clone E1L3N, Cell Signalling Technology) was used to analyse the TIM in six patients (pts) with resected NSCLC (full face section from block). Respective tissue microarrays were collected in triplicate from each specimen and underwent conventional IHC scoring for PD-L1, tumour infiltrating lymphocytes (TILs), CD8, FOXP3 and scored (0,1,2,3). The spatial arrangement of lymphocytes relative to tumour cells, stroma and PD-L1 expression was examined.

      Result:
      All six pts had adenocarcinoma histology, with the following level of PD-L1 expression: low(0-5%;n=2), intermediate(5-50%;n=2) and high(>50%;n=2)Figure1. In PD-L1[hi] pts Vectra staining showed uniform staining of PD-L1 across the full face. CD8 lymphocytes were present mainly in tertiary lymphoid structures without evidence of clustering. In PD-L1[lo] pts, one had heterogenous staining of TILs with dense stromal clustering (3:1 ratio of stroma to intratumoural). Neither patient (PD-L1[lo]) demonstrated significant PD-L1 uptake on full section assessment. Of the PD-L1[int] pts, although heterogeneity in PD-L1 expression was evident across the full face, the majority of tumour rich areas stained positively and TILs were uniform in the stroma. FOXP3 had low expression across all 6 patients <1% almost uniformly in the stroma.Figure 1



      Conclusion:
      Although PD-L1 staining heterogeneity was limited in this small dataset, clear differences in immune-cell infiltrate were seen between full-face sections and limited cores. Multiplex Immunofluorescent IHC provides accurate quantification of immune infiltrates and spatial alterations within the TIM and may facilitate predictive biomarkers.

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