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Y. Hirami
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MO19 - Lung Cancer Immunobiology (ID 91)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
- Moderators:Y. Sekido, J. Minna
- Coordinates: 10/30/2013, 10:30 - 12:00, Bayside 201 - 203, Level 2
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MO19.05 - EGFR signaling effects on NK cell-mediated cytotoxicity via NKG2D ligands-NKG2D interaction in non-small cell lung cancer cells (ID 2221)
10:55 - 11:00 | Author(s): Y. Hirami
- Abstract
- Presentation
Background
EGFR-tyrosine kinase inhibitor Gefitinib interrupts signaling through the EGFR in non-small-cell lung cancer (NSCLC) cells with EGFR driver mutation and has shown impressive activity in terms of clinical benefit for patients with NSCLC, however, almost all patients develop resistance to this drug. Although much research is focusing on the mechanisms of drug resistance in tumor cell, the role of EGFR signaling in tumor escape from the host immune system is poorly understood. NK cell activity is promoted via NK group 2, member D (NKG2D) on NK cells. The engagement between NKG2D and its ligands enhances cell-mediated cytotoxicity and cytokine production against transformed cells. Both MHC class I-related chain A and B (MICA/B) and UL16 binding protein (ULBP)s are expressed by intestinal epithelial and at low levels also by other non-malignant cell types. Primary tumor cells and tumor cell lines frequently express NKG2D ligands, but the mechanisms responsible for the induction of NKG2D ligands during oncogenesis are also poorly understood. Here we demonstrate Gefitinib downregulates NK group 2 member D (NKG2D) ligand MICA/B and ULBPs, resulting in attenuation of NK cell-mediated cytotoxicity in NSCLC cells.Methods
Possible influences of Gefitinib on expressions of MHC class I, MICA/B and ULBP1-3 in 5 NSCLC cell lines (A549, PC-9, RERF-LC-KJ, RERF-LC-AI, and LC2/ad) were investigated by flow cytometry. We also assessed whether genetic silencing of EGFR using siRNA of EGFR affected on the expression of NKG2D ligands. To ask the main downstream pathway of EGFR regulating the expression of NKG2D ligands, the cells were treated with PI3K-AKT inhibitor LY294002 or MEK inhibitor PD98059 then the expression of NKG2D ligands was analyzed. NK cell-mediated cytotoxicity against cancer cells was assessed by [51]Cr release assay or flow cytometry based CD107a degranulation assay.Results
Gefitinib downregulated NKG2D ligands in NSCLC cell lines. In line with these results, siRNA-mediated silencing of EGFR downregulated the expression of NKG2D ligand. Among the major downstream pathways activated by EGFR signaling, the expression of NKG2D ligands was mainly regulated by the PI3K-AKT pathway. Treatment with EGF promoted MICA/B expression in 2 of 5 cell lines, while EGF decreased MICA/B in 1 of 5 cell lines. These observations further emphasize that EGFR signaling is one of the major pathways regulating the expression of NKG2D ligands in NSCLC cells. As expected, inhibition of EGFR signaling-downregulated NKG2D ligands attenuated NK cell-mediated cytotoxicity.Conclusion
We conclude that EGFR signaling directly regulates the expression of NKG2D ligands and that this may influence the recognition of tumor cells by the innate immune system.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.19 - Poster Session 1 - Imaging (ID 179)
- Event: WCLC 2013
- Type: Poster Session
- Track: Imaging, Staging & Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.19-009 - Differences in proliferation of tumor cells in ground-glass opacity lesions on computed tomography for primary non-small cell lung cancer (ID 2801)
09:30 - 09:30 | Author(s): Y. Hirami
- Abstract
Background
Ground-glass opacities (GGOs) on computed tomography (CT) represent a distinctive finding for nodules of bronchioloalveolar carcinoma that are generally stable or growing very slowly due to a low degree of malignancy. Therefore, small GGOs are often followed conservatively. However, some GGO nodules undergo clear enlargement during follow-up. The present study aimed to define the clinical features of GGO with potentially high degree of malignancy.Methods
Among patients who underwent surgery for non-small cell carcinoma between June 2010 and April 2013 in our hospital, all 28 patients with GGO or mixed GGO nodules who had been prospectively evaluated with high-resolution computed tomography (CT) were enrolled in this study. Immunohistochemical studies using MIB-1 antibody to evaluate cell proliferation were performed using specimens obtained from GGO parts of 6 pure GGO and 22 mixed GGO nodules. A high-proliferation group was defined as cases showing >10% positive cells. The following clinical parameters were assessed: sex; age; smoking history; tumor size; tumor shape; tumor contour; ratio of consolidation area to whole area of tumor; and density of GGO. Correlations between high-proliferation status and clinical parameters were analyzed using Fisher’s exact probability test.Results
Median frequency of positive cells by immunohistochemistry for MIB-1 was 9% (range, 1-42%) and the high proliferation group comprised 10 cases (35.7%). This group correlated significantly with high-density GGO, defined as showing a difference >400 Hounsfield units between the GGO field and adjacent lung field (P=0.038), and tended to correlate with tumor diameter >20 mm (P=0.095).Conclusion
Density of GGO lesions correlates with proliferation of tumor cells. This clinical feature appears likely to allow differentiation of high-risk patients with GGO lesions.
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P2.07 - Poster Session 2 - Surgery (ID 190)
- Event: WCLC 2013
- Type: Poster Session
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.07-036 - Lower-than-expected FEV1 after upper lobe resection for lung cancer in the early postoperative period (ID 3039)
09:30 - 09:30 | Author(s): Y. Hirami
- Abstract
Background
After pulmonary resection, the immediate postoperative observed forced expiratory volume at 1 second (FEV1) is expected to be more correlated with the incidence of postoperative complications than the postoperative predicted FEV1. However, the clinical factors that affect the decrease in postoperative FEV1 have not been reported in detail.Methods
Seventy patients who underwent lobectomy or segmentectomy for lung cancer were prospectively enrolled in this study. Of these patients, 25 who performed all pulmonary function tests in the preoperative period and in the early (at 3 or 4 days), middle (3 weeks later), and late (> 3 months later) postoperative periods were analyzed. At each postoperative period, the ratio of the postoperative observed FEV1 to the postoperative predicted FEV1 (po/ppFEV1) was evaluated according to the clinical factors.Results
The mean po/ppFEV1 in the early / middle / late postoperative periods in all cases was 0.83 / 1.02 / 1.11. In the early period, the mean po/ppFEV1 of the resected upper / middle/ lower lobes was 0.74 / 0.97 / 0.88. The early poFEV1 after upper lobe resection was significantly lower than the ppFEV1 after middle or lower lobe resection (P=0.019). In the middle and late periods, no significant relationships were found between po/ppFEV1 and the resected lobe. No other clinical factors showed significant relationships with po/ppFEV1 in any postoperative period. The postoperative forced volume capacity (FVC) did not show a significant relationship with any clinical factor.Conclusion
Resection of the upper lobe leads to a decrease of the FEV1 in the early postoperative period that is lower than the postoperative predicted FEV1. Therefore, in the early postoperative period after upper lobe resection, careful management is needed in order to avoid pulmonary complications.
