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Jia Yu



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    MA04 - Models and Biomarkers (ID 122)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Biology
    • Presentations: 1
    • Now Available
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      MA04.02 - Molecular Profiling of Adenocarcinoma and Squamous Cell Lung Cancer at Single Cell Resolution (Now Available) (ID 1358)

      13:30 - 15:00  |  Author(s): Jia Yu

      • Abstract
      • Presentation
      • Slides

      Background

      Adenocarcinoma and squamous are two main subgroups of lung cancer: adenocarcinoma (ADC) accounts for 30-50% and squamous cell carcinoma (SCC) accounts for nearly 30% of all cases respectively. ADC and SCC have different pathological phenotypes and respond differently to various therapies, including immunotherapy. However, the underlying molecular mechanism of such differentiated drug responses still needs to be further characterized.

      Method

      To achieve high resolution of both tumor cells and their tumor microenvironment (TME), we used single cell RNA sequencing method to characterize ADC and SCC tumors from Stage IV NSCLC patients. Tissue biopsy samples from 21 patients (12 patients with ADC, 9 with SCC) were collected. For each sample, single cell RNA sequencing was performed on an average of 1930 cells. A graph-based clustering approach was used to classify cells into different cell types based on their gene expression patterns. The cellular subtypes of both cancer cells and TME in ADC and SCC samples were analyzed.

      Result

      ADC and SCC show distinct patterns at single cell resolution. Cancer cells from all ADC patients form two closely related clusters, while cancer cells from SCC patients show high intra-and inter-patient heterogeneity. Gene Ontology (GO) analysis demonstrated that ADC samples are enriched in genes of neutrophil degranulation and activation, while SCCs are enriched in genes related to epidermal cell differentiation and glutathione metabolic process. Genes related to cancer progression and metastasis, such as LSD1 and FASCIN, are normally expressed at higher level in SCC than in ADC. Furthermore, ADC samples contain higher percentage of a specific myeloid cell population, while SCC has higher percentage of fibroblasts, demonstrating the difference also in TMEs of ACD versus SCC.

      Conclusion

      The significantly higher level of heterogeneity for SCC can be a possible reason for poor responses to standard lung cancer therapies, including immunotherapy. Accurate characterization of SCC with single cell resolution could hold the key to more effective therapeutic strategies.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-62 - Association of Baseline Pulmonary Fibrosis with the Outcome of PD-1 Inhibitor in Patients with Advanced Non-Small Cell Lung Cancer (ID 2942)

      09:45 - 18:00  |  Author(s): Jia Yu

      • Abstract

      Background

      PD-1/PD-L1 inhibitors have become standard care for previously treated advanced non-small cell lung cancer (NSCLC). However, not all patients are suitable for the immunotherapy. This study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors in patients with advanced NSCLC and pre-existing pulmonary fibrosis (PF).

      Method

      Patients who had a NSCLC diagnosis, received anti-PD-1/PD-L1 monotherapy and had baseline chest HRCT screen at Shanghai Pulmonary Hospital, Tongji University were retrospectively collected from January 2016 to February 2019. The pre-existence of PF was identified by reviewing baseline chest imaging. Baseline clinicopathologic characteristics, treatment outcomes and immune-related pneumonitis were collected.

      Result

      116 patients were included with 61 age < 65. Among them, 97 (83.6%) were male, 76 (65.5%) were smoker, 51 (44%) were squamous, 61 (52.6%) received anti-PD-1 monotherapy (Pembolizumab n=62, Nivolumab n=28) as 2nd line setting, 28 (24.1%) had PF prior to PD-1 inhibitors. Baseline characteristics such as age, gender, ECOG PS, smoking history, pathology are similar between patients with or without PF. Patients with PF had a comparable response (ORR: 25% vs 15.9%, p=0.277, figure A), disease control (DCR: 60.7% vs 48.9%, p=0.274, figure B) and PFS (median 2.5 vs 2.8 months, p=0.950). The incidence of immune-related pneumonitis in the entire cohort was 9.2%, which was numerally higher in PF group (17.9% vs 6.8%, p=0.172, figure C). No death from immune-related pneumonitis occurred.

      fig.jpg

      Conclusion

      NSCLC patients with pre-existing PF showed comparable response to PD-1 inhibitors but a higher incidence to immune-related pneumonitis.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-30 - Hepatitis B Infection or Aminotransferase Increase Associate with Poor Outcome of Anti-PD-1 Monotherapy in Patients with Advanced NSCLC (ID 2508)

      10:15 - 18:15  |  Author(s): Jia Yu

      • Abstract

      Background

      Previous study demonstrated that the existence of liver metastases at the commencement of immunotherapy was associated with poor response. Since hepatitis B infection and liver dysfunction were higher prevalent in China, this study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitor in Chinese NSCLC patients with hepatitis B infection or liver dysfunction.

      Method

      We retrospectively collected the patients who were diagnosed with non-small cell lung cancer and received anti-PD-1 monotherapy at Shanghai Pulmonary Hospital, Tongji University School of Medicine, China, from January 2016 to February 2019. Detailed clinicopathologic characteristics, therapeutic outcomes, hepatitis biomarker test and liver function test were collected.

      Result

      135 patients were enrolled with 73(54.1%) aged <65 years old. Among them, 113(83.7%) were male, 84(62.2%) were smoker, 57(42.2%) were squamous, 69(44.4%) received anti-PD-1 monotherapy (Pembolizumab n=28, Nivolumab n=21) as 2nd line setting, 5(3.7%) patients had hepatitis B infection and 17(12.6%) had increased ALT or AST. The baseline characteristics such as age, gender, smoking status, histology, PD-1 mono-antibodies, line of therapy was similar between hepatitis infection or liver dysfunction group vs. normal group. Hepatitis infection or liver dysfunction group had a lower ORR (9.5% vs. 17.5%, p=0.553, Figure A), significantly shorter PFS (1.6 months vs. 3.0 months, p<0.050, Figure B) when compared with these patients without. Out of the 22 patients with hepatitis or increase transaminase, 35.7% deteriorated the grading of alanine or aspartate aminotransferase increased. 肝炎肝损final (1).jpg

      Conclusion

      NSCLC patients with hepatitis B infection or increased transaminase showed a high incidence of hepatic disfunction and poor outcome to anti-PD-1 monotherapy.