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Huimin Wang



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    OA07 - Oligometastasis: What Should Be the State-Of-The-Art? (ID 905)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 107
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      OA07.06 - Efficacy of Local Consolidative Therapy for Oligometastatic Lung Adenocarcinoma Patients Harboring EGFR Mutations. (ID 12523)

      16:10 - 16:20  |  Author(s): Huimin Wang

      • Abstract
      • Presentation
      • Slides

      Background

      For oligometastatic lung adenocarcinoma patients with sensitive EGFR mutations, the role of local consolidative therapy (LCT) remains debatable. The purpose of this study was to investigate the efficacy of LCT in these patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Advanced stage patients with oligometastatic lung adenocarcinoma who harboring EGFR mutation were identified at the Shanghai Chest Hospital from 2010 to 2016.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 253 patients (149 patients who received LCT plus EGFR-TKIs [combination group] and 104 patients who received EGFR-TKIs [TKI monotherapy group] were included. The median PFS time in the combination group was 14 months versus 9 months in the TKI monotherapy group (HR=0.57, 95% [CI] 0.44, 0.79, p<0.01, Figure 1 A). The median OS time in the combination group was 33 months versus 20 months in the TKI monotherapy group (HR=0.56, 95% [CI] 0.41, 0.75, p<0.01, Figure 1D). Survival benefit was independent of EGFR mutation type (PFS: 19del, p=0.02, Figure 1B; 21L858R, p<0.01, Figure 1C; OS: 19del, p=0.0189, Figure 1E; 21L858R, p<0.01, Figure 1F) and metastatic sites .figure 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      LCT combined with TKI therapy was feasible and significantly improved PFS and OS among oligometastatic lung adenocarcinoma patients with sensitive EGFR mutations, and thus, should be considered as an important medical treatment during clinical management.

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-22 - OCT4&amp;SOX2 Specific CTLs Plus PD-1 Inhibitor Had Synergistic Effect on Killing CSC And Treating Drug-Resistant Lung Cancer Mice (ID 12402)

      16:45 - 18:00  |  Author(s): Huimin Wang

      • Abstract
      • Slides

      Background

      This study aimed to investigate the synergistic effect of OCT4&SOX2 specific cytotoxic T lymphocytes (CTLs) and PD-1 inhibitor on killing lung cancer stem-like cells (LCSCs) and their efficacy in treating drug-resistant lung cancer (DRLC) mice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      OCT4&SOX2 specific CTLs and PD-1 inhibitor with differed doses were applied to treat PC9 cells and PC9 LCSCs. CCK8 assay and flow cytometry (FCM) assay with CFSE staining target cells before treatment and PE staining died cells after treatment were conducted to detect the cytotoxic activity. DRLC mice were constructed by injection of PC9 LCSCs suspension and Matrigel into left lung of SD mice. DRLC mice was randomly divided into 5 group: Control group, CMV pp65 CTLs group, OCT4&SOX2 CTLs group, PD-1 inhibitor group and OCT4&SOX2 CTLs+PD-1 inhibitor group.

      4c3880bb027f159e801041b1021e88e8 Result

      In vitro, Both CCK8 assay and FCM assay disclosed that OCT4&SOX2 specific CTLs plus PD-1 inhibitor presented with elevated cytotoxic activity on PC9 cells and PC9 LCSCs. In vivo, tumor volume and tumor weight were decreased, while tumor necrosis and tumor apoptosis were increased in OCT4&SOX2 CTLs group than CMV pp65 CTLs group and control group, and in OCT4&SOX2 CTLs+PD-1 inhibitor group than OCT4&SOX2 CTLs group and PD-1 inhibitor group. In addition, CD8 expression was increased while OCT4 and SOX2 expressions were decreased in OCT4&SOX2 CTLs+PD-1 inhibitor group than OCT4&SOX2 CTLs group and PD-1 inhibitor group.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, OCT4&SOX2 specific CTLs and PD-1 inhibitor presented with synergistic effect on killing LCSCs in vitro and treating DRLC mice in vivo.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P2.03-37 - The Efficiency of Octamer-4 Specific Cytotoxic T Cells Induce By CD40-B Cells in Killing Lung Cancer Stem-Like Cells (ID 12399)

      16:45 - 18:00  |  Author(s): Huimin Wang

      • Abstract
      • Slides

      Background

      This study aimed to investigate the correlation of Octamer-4 (OCT4) expression with clinicopathological features and prognosis in lung adenocarcinoma patients, and to further explore the killing effect of OCT4 specific cytotoxic T cells (CTLs) on lung cancer stem cells (LCSCs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      257 lung adenocarcinoma patients underwent thoracic surgery were enrolled in this study and tissue samples were obtained during the operation. OCT4 expression was detected by immunofluorescence staining assay. CD154+ feeder cells were constructed to transfect CD40-B cells, and then mixed with OCT4 antigen peptides and CD8+ T lymphocytes extracted from peripheral blood of lung adenocarcinoma patients, subsequently the OCT4 specific CTLs were co-cultured with PC9 LCSCs to detect the killing efficacy. OCT4+ phenotype was illuminated to be associated with poor differentiation, worse disease free survival (DFS) and overall survival (OS). And Cox’s analysis revealed OCT4+ was an independent predictive factor for shorter DFS and OS.

      4c3880bb027f159e801041b1021e88e8 Result

      CD40-B-cells with antigen presenting capacity was successfully constructed indicated by elevated CD86+, human leukocyte antigens (HLA)-A+ and CD80+ cells percentage, and OCT4 specific CTLs was successfully activated suggested by increased CD3+, CD4+ and CD8+ cells percentage as well as elevated interleukin (IL-2) and interferon (IFN)-γ expressions. OCT4 specific CTLs presented an elevated cytotoxic activity on LCSCs at percentage 75.5% ± 8.2% compared with CMV pp65 CTLs (25.6% ± 5.1%) and blank control CTLs (20% ± 4.7%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, OCT4 expression could be served as a convincing risk biomarker for prognosis in lung adenocarcinoma patients and potential target of CTLs as immuntherapy in killing LCSCs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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