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A. Maeda
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-028 - Prognostic Value of Cox-2 Expression Differs Depending on CD8+ T Lymphocytes and PD-L1 Expression in Resected Lung Adenocarcinoma (ID 8108)
09:30 - 09:30 | Author(s): A. Maeda
- Abstract
Background:
Programmed cell death-1 ligand 1 (PD-L1), tumor infiltrating CD8-positive T lymphocytes (CD8+TILs), and cyclooxygenase-2 (Cox-2) has been used as a prognostic tool in lung adenocarcinoma.
Method:
We conducted a retrospective review of data from 170 patients who underwent pulmonary resection as the first treatment for clinical T1-2 N0 lung adenocarcinoma. We investigated the expressions of three biomarkers and EGFR mutation, and analyzed between expression levels and clinicopathological characteristics or prognosis. Then we classified tumors into four groups based on PD-L1 and CD8+TILs status, and evaluated the prognostic significance of Cox-2 expression according to tumor immune-microenvironment classification.
Result:
The high PD-L1 expression tumors showed a significantly larger number of CD8+TILs than low PD-L1 tumors, in contrast, the high Cox-2 expression tumors showed significantly fewer CD8+TILs than low Cox-2 tumors. A multivariate analysis showed that histological subtype, nodal metastasis, CD8+TILs count, and the PD-L1 expression were independent predictor of recurrence-free survival. Based on the classification of PD-L1 and CD8+TILs status, the prognosis in patients with low PD-L1 and high CD8+TILs was significantly better than other types. In patients with low PD-L1 and low CD8+TILs, the rate of EGFR mutation was significantly higher than other types and Cox-2 expression was a powerful predictor of prognosis.
Conclusion:
Clinical and pathological features in conjunction with tumor immune-microenvironment classification indicate that lung adenocarcinoma should be divided into different subgroups. The classification of PD-L1 and CD8+TILs status might predict the effect for immunocheckpoint inhibitors, EGFR tyrosine kinase inhibitors, and/or Cox-2 inhibitor.
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P2.02-031 - Relationship between PD-L1 Expression and EGFR/HER2 Signaling in Non-Small-Cell Lung Cancer (ID 8697)
09:30 - 09:30 | Author(s): A. Maeda
- Abstract
Background:
Immunocheckpoint inhibitors targeting PD-1/PD-L1 axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). It is well known that PD-L1 is induced by IFNg, however recent study shows that EGFR also affects PD-L1 expression in tumor cells.
Method:
We evaluated the expressions of PD-L1, EGFR, and HER2 in tumor tissues collected from patients with pStage IA–IIIA NSCLC using immunohistochemistry. Intensity scoring for staining was calculated with H-score (0-300). The relationships between their expression and clinicopathological characteristics were evaluated. For in vitro assay, the expression of PD-L1 was evaluated by flow cytometric analysis while cell signaling pathways were assessed with Phospho-Receptor Tyrosine Kinase (RTK) array in LC2/ad human lung adenocarcinoma cell line.
Result:
Of the total 91 tumors, 13 cases (14%) showed PD-L1 overexpression, 12 cases (13%) showed EGFR overexpression, and 35 cases (38%) showed HER2 overexpression in tumor cells. PD-L1 overexpression associated with poor clinical outcome and was positively correlated with EGFR expression while inversely correlated with HER2. To assess the regulation mechanism of PD-L1 expression via EGFR/HER2 signaling, LC2/ad cells were treated with EGF with or without inhibition of EGFR or HER2, after which PD-L1 expression was evaluated using flow cytometry. Consistent with previous reports, PD-L1 expression was clearly enhanced by EGF, and either EGFR-tyrsine kinase inhibitor Gefitinib and siRNA for EGFR blocked EGF-induced PD-L1 overexpression in LC2/ad cells. On the other hand, we found that siRNA for HER2 could not block EGF-induced PD-L1 overexpression. We compared EGF-induced signaling with IFNg-induced one by RTK array, and found EGF stimulation activated AKT, MAPK, and S6 ribosomal protein while IFN-g activated STAT1.
Conclusion:
PD-L1 overexpression is associated with poor prognosis and is positively correlated with EGFR expression but inversely correlated with HER2 expression in NSCLC. The expression mechanism of PD-L1 is different between EGFR and HER2 signaling in LC2/ad cell line. Additionally, both EGF and IFNg enhance PD-L1 expression but via different pathway in NSCLC cell line LC2/ad.
