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Kazuki Takada
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OA 13 - Immuno-Biology (ID 677)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Hiroyuki Suzuki, Scott N. Gettinger
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 301 + 302
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OA 13.06 - Co-Expression of IDO1 and PD-L1 Indicates More Aggressive Features of Lung Adenocarcinoma (ID 9672)
11:55 - 12:05 | Author(s): Kazuki Takada
- Abstract
- Presentation
Background:
Indoleamine 2, 3-dioxygenase 1 (IDO1) serves as an immunosuppressive effector and it is closely related to the prognosis in several types of cancer. We herein aim to elucidate the clinicopathological features and prognoses in patients with IDO1-expressing lung adenocarcinoma, and especially, show its correlation with the expression of programmed cell death-ligand 1 (PD-L1).
Method:
The expressions of IDO1 and PD-L1 proteins in 427 patients with surgically resected primary lung adenocarcinoma were evaluated by immunohistochemical analyses and any associations identified between IDO1 and the clinicopathological features, the prognosis and co-expression of IDO1 with PD-L1 were investigated. The expressions of IDO1 and PD-L1 at the protein and mRNA levels in lung adenocarcinoma cell lines were examined by an Enzyme-Linked Immuno Sorbent Assay, flow cytometry, and reverse transcription and real-time PCR analysis, respectively.
Result:
IDO1 was expressed in 260 patients (60.9%) at a 1% cut-off and in 63 patients (14.8%) at a 50% cut-off, respectively. PD-L1 was positive for 145 patients (34.0%). A ultivariate analysis showed IDO1 positivity (1% cut-off) to be significantly associated with a higher tumor grade, the presence of vascular invasion, and the expression of PD-L1. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and the patients whose tumor expressed both proteins exhibited significantly higher malignant traits than those whose tumor expressed only one protein or none. According to a multivariate analysis, the co-expression of both proteins was significantly associated with a shorter disease-free survival and overall survival. The expressions of IDO1 and PD-L1 in lung adenocarcinoma cell lines were elevated by treating them with interferon-γ and transforming growth factor-β.Figure 1
Conclusion:
The findings of this study suggest that the co-expression of IDO1 and PD-L1 may indicate more aggressive features of lung adenocarcinoma. Combination therapy targeting both of these proteins may therefore improve the clinical outcomes in patients with lung adenocarcinoma.
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-002 - The Expression of PD-L1 Protein as a Prognostic Factor in Lung Squamous Cell Carcinoma (ID 7345)
09:30 - 09:30 | Presenting Author(s): Kazuki Takada
- Abstract
Background:
Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy has become the standard option of care in the management of lung cancer. The expression of the PD-L1 protein in lung cancer is expected to be a prognostic factor or to predict the response to PD-1-blocking antibodies. However, the association between PD-L1 positivity and the clinicopathological features and patient outcomes in lung squamous cell carcinoma (SCC) remains unclear because the definitive cut-off value for the expression of PD-L1 protein remains to be established.
Method:
The expression of PD-L1 protein in 205 surgically resected primary lung SCC patients was evaluated by immunohistochemistry with the antibody clone SP142. We generated a histogram to show the proportion of PD-L1-positive carcinoma cells as described in the figure below, and set the cut-off values as 1%, 5%, 10% and 50%. Moreover, we examined the proliferative capacity of these tumors using Ki-67 immunohistochemistry.Figure 1
Result:
The samples from 106 (51.7%), 72 (35.1%), 61 (29.7%) and 37 (18.0%) patients were positive for the expression of PD-L1 protein at cut-off values of 1%, 5%, 10% and 50%, respectively. Fisher’s exact test showed that, for almost all of the factors, PD-L1 positivity was not associated with the clinicopathological features with any of the four cut-off values. Univariate and multivariate survival analyses revealed that the PD-L1-positive patients only had a poorer prognosis than the PD-L1-negative patients at the 1% cut-off value. The Ki-67 labeling index in the PD-L1-positive patients was higher than that in the PD-L1-negative patients.
Conclusion:
The expression of PD-L1 protein was associated with a poor prognosis in lung SCC patients. The 1% cut-off value for PD-L1 might become a better predictive marker than the other cut-off values, and notably, even minimal expression of PD-L1 protein may have a negative prognostic significance.
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P1.07-014 - Association of Preoperative Serum CRP with PD-L1 Expression in NSCLC: A Comprehensive Analysis of Systemic Inflammatory Markers (ID 8909)
09:30 - 09:30 | Author(s): Kazuki Takada
- Abstract
Background:
Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients. Therefore, here we investigated the potential association of PD-L1 expression with systemic inflammatory markers, including CRP, NLR, lymphocyte-monocyte ratio and platelet-lymphocyte ratio.
Method:
We retrospectively examined tumor PD-L1 expression in 508 surgically resected primary NSCLC cases by immunohistochemical analysis (cut-off value: 1%). The association of PD-L1 expression with preoperative systemic inflammatory markers was assessed by univariate and multivariate analyses. We generated a PD-L1 association score (A-score) from serum CRP level (cut-off value: 0.3 mg/dl) and smoking status to predict PD-L1 expression.
Result:
Among the total 508 patients, 188 (37.0%) patients were positive for PD-L1 expression at the 1% cut-off value and 90 (17.5%) had elevated serum CRP level. Multivariate logistic regression revealed that that PD-L1 positivity was significantly associated with advanced stage, the presence of vascular invasion and high serum CRP level (P=0.0336, 0.0106 and 0.0018, respectively). Though not significant, smoking history tended to be associated with PD-L1 protein expression (P=0.0717). There was no correlation with other inflammatory markers. Smoking history with elevated CRP level (A-score: 2) was strongly associated with PD-L1 protein expression (odds ratio: 5.18, P<0.0001), while it was inversely associated with EGFR mutation (odds ratio: 0.11, P<0.0001).
Conclusion:
Our results indicate that among all systemic inflammatory markers examined, serum CRP level could be a helpful biomarker for PD-L1 expression that is easily determined and available worldwide.
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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-003 - The Clinical Significance of Immune-Nutritional Parameters in Surgically Resected Elderly Patients with Non-Small Cell Lung Cancer (ID 7403)
09:30 - 09:30 | Author(s): Kazuki Takada
- Abstract
Background:
The world’s population is rapidly aging, and the age of patients with lung cancer will increase as well. The prognostic nutritional index (PNI), controlling nutritional status (CONUT), and the geriatric nutritional risk index (GNRI) are useful parameters for evaluating immune-nutritional status. We aimed to perform a multicenter retrospective study to investigate the correlations of these immune-nutritional parameters with postoperative comorbidities or surgical outcomes of elderly patients with non-small cell lung cancer (NSCLC).
Method:
We selected 272 consecutive patients with NSCLC aged >75 years treated from January 2005 to December 2012 and evaluate three preoperative immune-nutritional parameters as potential predictive factors of postoperative comorbidities or as prognostic factors for surgically resected elderly patients with NSCLC.
Result:
Both PNI and GNRI as well as sex and preoperative respiratory comorbidities, were significantly associated with postoperative comorbidities (P =0.0287, 0.0443, 0.0191 and 0.0177, respectively). Multivariate analyses showed that preoperative GNRI (P = 0.0161) as well as sex (P < 0.0001), preoperative serum carcino embryonic antigen levels (P = 0.0128), preoperative serum cytokeratin 19 fragment levels (P = 0.0125), pleural invasion (P = 0.0214) and lymphatic vessel invasion (P = 0.0165) significantly affected overall survival (OS). Abnormal GNRI was significantly associated with histology (P = 0.0419) and outcome (P =0.0077). In Kaplan–Meier analysis of OS by preoperative GNRI, the abnormal GNRI group had significantly shorter OS than the normal GNRI group (5-year OS, 45.15% vs. 64.10%, P = 0.0007, log-rank test). CONUT score did not have any correlation with postoperative comorbidities or surgical outcome.
Conclusion:
Preoperative GNRI is a novel preoperative predictor of postoperative comorbidities as well as a prognostic factor that may identify high-risk elderly patients with NSCLC.
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P3.16-033 - Significance of Spread through Air Spaces in Resected Pathological Stage I Lung Adenocarcinoma (ID 9182)
09:30 - 09:30 | Author(s): Kazuki Takada
- Abstract
Background:
Spread through air spaces (STAS) is a novel invasive pattern of lung cancer, which spreads within air spaces beyond the edge of the main tumor, but not necessarily accompanying stromal invasion. In the current study, we investigated the significance of STAS in patients with pathological stage I adenocarcinoma.
Method:
STAS was assessed in a total of 276 patients with resected pathological stage I adenocarcinoma. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) using a 20x objective and a 10x ocular lens. We evaluated the association between STAS and the clinicopathological characteristics and postoperative survivals.
Result:
Among 276 patients, 123 (44.6%), 48 (17.4%) and 105 (38.0%) were classified as having no, low and high STAS, respectively. Fisher’s exact test demonstrated that positivity for STAS was significantly associated with a larger radiological tumor diameter (P=0.008), a higher consolidation/tumor ratio (P<0.001), a higher maximum standard uptake value (P<0.001), a pathologically larger tumor size (P=0.004), the presence of pleural invasion (P=0.027) and a histologically invasive type (P<0.001), while STAS was not significantly associated with epidermal growth factor receptor mutations or programmed death ligand-1 expression (P=0.129 and P=0.872, respectively). Patients with the STAS had significantly shorter recurrence-free and overall survivals than those without (P<0.001 and P=0.002, respectively). According to a multivariate analysis, positivity for STAS remained an independent prognostic parameter for both the recurrence-free and overall survivals.
Conclusion:
STAS was associated with clincopathologically invasive features and was predictive of a worse survival. Figure 1
