Author of

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  P2.04 - Immuno-oncology (ID 167)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Immuno-oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 31006

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    P2.04-55 - Tumor Spread Through Air Spaces Is Associated with the Non-Inflamed Immune Microenvironment in Lung Squamous Cell Carcinoma (ID 2529)

    10:15 - 18:15  |  Author(s): Chihiro Konoeda
    • Abstract

    Background
    

    Tumor spread through air spaces (STAS) is reportedly a poor prognostic factor in non-small cell lung cancer. However, little is known about the molecular background and tumor microenvironment associated with STAS. This study assessed the relationship between STAS and tumor microenvironment in lung squamous cell carcinoma using next generation sequencing data.

    Method
    

    RNA-sequencing and whole-exome sequencing were performed in 20 surgically resected lung squamous cell carcinoma cases. Pathological specimens were reviewed to determine the existence of STAS. Somatic mutations, gene expression and gene set enrichment were analyzed and compared between STAS positive and negative tumors.

    Result
    

    Among 20 patients, nine were pathological stage I, six stage II and five stage III. In all, eight tumors were positive for STAS and 12 were negative. While STAS was not associated with tumor size, all N2 tumors were positive for STAS. Tumor mutational burden was not associated with STAS.

    Hierarchical clustering using the single sample Gene Set Enrichment Analysis score of 4872 immunologic signature gene sets revealed two clusters (Figure 1). Cluster 1 revealed lower expression of immune-related genes, forming a cluster of non-inflamed (cold) tumors. The cluster of non-inflamed tumors showed a tendency to higher STAS positivity (Cluster 1, 67%; Cluster 2, 18%; p=0.065).

    Next, we performed Gene Set Enrichment Analysis between STAS positive and negative tumors. Using 50 Hallmark gene sets in the Molecular Signatures Database, gene sets of allograft rejection, IL2-STAT5 signaling, inflammatory response and complement were found to have a significantly lower expression in STAS positive tumors (q <0.05).

    We further investigated the expression of each immune-related gene and compared them between STAS positive and negative tumors, which showed that PD-L1 gene expression was significantly lower in STAS positive tumors (p=0.023).

    

    Conclusion
    

    STAS positivity was associated with the non-inflamed tumor-immune microenvironment in lung squamous cell carcinoma. Our findings might partly explain the aggressive behavior of STAS positive tumors. Since the efficacy of immunotherapy might differ between STAS positive and negative tumors, further investigation of immunological and molecular aspects of STAS positive tumors is needed.