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Takahiro Karasaki



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    MA19 - Genomic Markers of IO Response (ID 922)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
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      MA19.05 - Difference of Tumor Mutational Burden Is Associated with Distinct Immune Microenviroment in the T Cell-Inflamed Lung Adenocarcinoma (ID 13495)

      15:40 - 15:45  |  Presenting Author(s): Takahiro Karasaki

      • Abstract
      • Presentation
      • Slides

      Background

      PD-L1 expression on tumor cells, tumor infiltrating lymphocytes (TILs), and tumor mutational burden (TMB) have been reported as predictive biomarkers for checkpoint inhibitor immunotherapies. However, little is known about the relationship between each biomarkers. The aim of this study was to assess the relationship between these biomarkers, especially TIL and TMB.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      RNA-seq data of 533 primary lung adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA). Gene expression and gene set enrichment were analyzed. Clinical information and somatic missense mutation data were also integrated.

      4c3880bb027f159e801041b1021e88e8 Result

      Weak correlation between PD-L1 and CD8A expression (Spearman’s R=0.32, P<0.001), and PD-L1 expression and TMB (R=0.10, P=0.019) were seen, but not between CD8A expression and TMB (R=0.03, P=0.45). Next, we performed gene signature analysis related to cancer-immunity cycle (ref. Karasaki et al. J Thorac Oncol 2017). Hierarchical clustering resulted in 3 clusters: T cell non-inflamed phenotype with high antigenicity (Cluster 1), inflamed phenotype with low antigenicity (Cluster 2), and inflamed phenotype with high antigenicity (Cluster 3).(Fig.1) Compared with Cluster 3, Cluster 2 was featured by lower gene expression signature of cytolytic activity (P<0.0001, U-test), as well as lower expression of PD-L1 (P<0.0001, U-test).

      To further investigate the relationship between TMB and TILs, T-cell inflamed phenotype tumors were divided into four groups according to the quartiles of TMB. We estimated immune cell phenotypes of TMB-high (upper quartile) and TMB-low (lower quartile) groups using ssGSEA and CIBERSORT. Either analysis showed significant enrichment of activated CD4 T cells in TMB-high group (P<0.0001, T-test).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Existence of Cluster 1 and 2 suggested that tumor antigenicity (TMB) does not necessarily correlate with TIL enrichment. TMB-low tumors may form T cell-inflamed tumors (Cluster 2), although the immune status may differ from TMB-high inflamed tumors (Cluster 3). Integrating multiple biomarkers for the assessment of tumor immune microenvironment is important for optimal immunotherapy.

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    P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.16-40 - Impact of Preoperative Pectoralis Muscle Quantity and Density on Outcome After Complete Resection of Non-Small Cell Lung Cancer (ID 12135)

      16:45 - 18:00  |  Author(s): Takahiro Karasaki

      • Abstract
      • Slides

      Background

      Body composition measures may predict outcomes of cancer surgery. In this study we evaluated the prognostic significance of pectoralis muscle quantity and density in patients with surgical non-small cell lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Preoperative pectoralis muscle quantity and density were retrospectively assessed in 181 patients undergoing lobectomy and lymph node dissection for non-small cell lung cancer from 2009 to 2013. The pectoralis muscle index (cross-sectional area/height2) and density (average Hounsfield unit, HU) at the fourth thoracic vertebra level were measured and calculated on preoperative plain computed tomography. Overall survival was analyzed between the lowest gender-specific quartile of the pectoralis muscle index and density and the other quartiles.

      4c3880bb027f159e801041b1021e88e8 Result

      Positive correlations between pectoralis muscle index and density and body mass index (BMI) were identified in the cohort (Pearson's r=0.349, p<0.001; r=0.206, p=0.005, respectively). The gender-specific lowest quartile cut-off values of the pectoralis muscle index and density was 10.14cm2/m2 and 28.97HU for males, 7.86cm2/m2 and 21.23HU for females, respectively. The cumulative five-year overall survival rates were significantly shorter in patients with low pectoralis muscle index (51.7% vs. 76.0%, p=0.009), while for low pectoralis density (66.0% vs. 70.7%, p=0.391). The multivariate analysis including age, smoke index, BMI, c-reactive protein, carcinoembryonic antigen and pathologic stage revealed that the pectoralis muscle index, not the pectoralis density or BMI, was an adverse independent risk factor for overall survival (p=0.002, hazard ratio: 2.815, 95% confidence interval: 1.473–5.377).wclc image(300dpi)-illustration and survival curve for pectoralis muscle.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      A low preoperative pectoralis muscle index was associated with a poor postoperative outcome in surgical patients with non-small cell lung cancer. Pectoralis muscle quantity which is more predictive than density and BMI as a convenient measure, may be included in the preoperative assessment when surgical intervention is considered for non-small cell lung cancer.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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