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Lihui Liu



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    P60 - Tumor Biology and Systems Biology - Basic and Translational Science - Immune Bio (ID 198)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P60.03 - Identifying Patterns in Responses to PD-1 Immunotherapy for Patients With Squamous Cell Lung Cancer and Non-Squamous Cell Lung Cancer (ID 1537)

      00:00 - 00:00  |  Presenting Author(s): Lihui Liu

      • Abstract
      • Slides

      Introduction

      Lung cancer is associated with high morbidity and mortality, yet the emergence of immunotherapies offers hope for those in treatment. Research in this field has recently identified subtle differences in the efficacy of PD-1 monotherapy in patients with histologies of squamous cell lung cancer (LUSC) and non-squamous cell lung cancer (non-LUSC). Therefore, mapping different responses to PD-1 immunotherapy may pave the way to more individualized treatments and enhance the effect of interventions. Here, we aimed to identify the underlying mechanisms involved in PD-1 immunotherapy responses in patients with LUSC and non-LUSC.

      Methods

      We obtained expression profiles from 35 patients (GSE93157) who received PD-1 immunotherapy from the Gene Expression Omnibus (GEO) database. By using hallmark gene sets and all curated gene sets as references, we performed Gene Set Enrichment Analysis (GSEA) between responders and non-responders with LUSC and compared findings with the non-LUSC sample. A nested comparison using the following algorithm: (LUSC_response vs. LUSC_non-response) versus (non-LUSC_response vs. non-LUSC_non-response) was performed, setting the significance threshold to p < 0.05 and the log2 Foldchange to >1.0 in order to identify differentially expressed genes (DEGs). Functional annotation was performed using DAVID 6.8 online tool.

      Results

      GSEA results revealed that the enrichment of epithelial mesenchymal transition (EMT) signaling pathway is significant, positively correlating with responses to PD-1 immunotherapy in patients with LUSC. By contrast, patients with non-LUSC who received EMT signalling pathway enrichment showed no response to PD-1 treatment. Additionally, the IL4 pathway appears to be significant in PD-1 immunotherapy responses. Both LUSC and non-LUSC patients showed improved responses to PD-1 treatment when the IL4 pathway was upregulated. Nested comparisons identified 12 DEGs within our sample of LUSC and non-LUSC patients, which might provide reasons for the different responses to PD-1 immunotherapy. Gene Ontology (GO) term analysis also indicates that the 12 DEGs significantly correlate with immune responses, lymphocyte activation, B cell activation, cytokine activity, and chemokine activity.figure.png

      Conclusion

      Through data mining, we identified different PD-1 immunotherapy response patterns in patients with LUSC and non-LUSC, including EMT signaling and IL4 pathways. We also identified 12 DEGs as PD-1 response-related genes which require further investigation but may influence both LUSC and non-LUSC patient prognoses.

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