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S.R. Knight
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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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 - 09:30 | Author(s): S.R. Knight
- Abstract
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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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-052 - Use of Decellularised Porcine Intestinal Submucosa Extracellular Matrix in Airway Reconstruction to Enable Lung-Sparing Oncological Surgery (ID 9639)
09:30 - 09:30 | Author(s): S.R. Knight
- Abstract
Background:
Reconstruction of the airways following tracheal resection, tracheo-oesophageal complications and lung-sparing oncological surgery is challenging. Airway reconstruction materials ideally must possess balanced properties of rigidity, flexibility and have an intact surface of epithelium to maintain a functional airway. A novel approach is the use of bio-scaffolds which allow regeneration of respiratory epithelium and eliminate the need for immunosuppressive treatment. Initial experiences with decellularised porcine small intestine submucosa extracellular matrix (CorMatrix®) as a scaffold for vascular, cardiac and pericardial tissue repair and reconstruction has been encouraging. The properties of extracellular matrix are potentially suitable for airway reconstruction.
Method:
We initially used the bio-scaffold for repairing tracheal defects and tracheo-oesophageal fistulae (n=6). We then extended its use to reconstruct distal airways to facilitate lung-sparing oncologic resections of intermediate grade lung tumours (n=3). These patients would otherwise have required pneumonectomy (Case 1 and 2) or bi-lobectomy in a patient with borderline lung function (Case 3). We describe our experience using extracellular matrix for airway reconstruction in lung-sparing oncological surgery.
Result:
Three patients underwent complex sleeve resections with varying degrees of bronchial airway reconstruction using extracellular matrix. The lung tumours were: (1) muco-epidermoid tumour of the left upper lobe and left main bronchus; (2) typical carcinoid of the right main bronchus; (3) typical carcinoid of the intermediate bronchus and right middle lobe. All patients underwent frozen section pathology examination at the time of surgery and formal histology confirmed pT1N0 and R0 resection status. There were no perioperative complications. All patients underwent bronchoscopy prior to discharge and serial bronchoscopies were carried out 6 weeks, 3 months and at >1 year. All patients had complete integration of the scaffold by epithelialisation and the patch was not evident at 3 months. All segmental bronchi were widely patent. At 18 months there was no tumour recurrence.
Conclusion:
The use of decellularised porcine intestinal submucosa extracellular matrix (CorMatrix®) as a bio-scaffold is safe and shows remarkable epithelialisation and integrity. It is an option for airway reconstruction to facilitate lung-sparing surgery without compromising oncologic margins.
