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Daisei Yasuda

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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-07 - Correlation Between PD-L1 Expression and Expression of CDK4 and SPOP in Non-Small Cell Lung Cancer (ID 12747)

      12:00 - 13:30  |  Author(s): Daisei Yasuda

      • Abstract
      • Slides


      Immunotherapy that targets programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has emerged as a novel treatment modality for cancers. Clinical trials have reported durable responses and long-term remissions using PD-1/PD-L1 inhibitors, and the expression level of PD-L1 at the tumor cells was correlated with a response to PD-1/ PD-L1 inhibitors. However these inhibitors are only effective in a subset of lung cancer patients, and the underlying molecular mechanisms are not well understood. Recently, it has been reported that PD-L1 expression can be regulated at both transcriptional and post-translational levels, such as cyclinD-CDK4 and the cullin 3-SPOP (phosphorylation of speckle-type POZ protein) E3 ligase. In this study, we focus on the regulation of PD-L1 expression in lung cancer, and we investigated the association between the expression of PD-L1 and biomarkers in regard to clinical outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We invested CDK4, CDK6 and SPOP expression of lung cancer, and CD4 and CD8 expression of tumor-infiltrating lymphocytes (TILs) by immunohistochemistry of 36 non-small cell lung cancers, those had undertaken an operation or chemotherapy from March 2007 to January 2018 and analyzed PD-L1 expression (negative:0%, low expression:1-49%, high expression:≥50%). The staining intensity of CDK4, CDK6 and SPOP was scored as 0 (negative), 1 (weak), 2 (medium), and 3 (strong). Extent of staining was scored as 0 (0-10%), 1 (11-25%), 2 (26-50%), 3 (51-75%), and 4 (76-100%) according to the percentages of the positive staining areas in relation to the whole cancer area. For CD4+ and CD8+ cells, a maximum numbers of stained cell were counted semi-quantitatively in high-powered fields for the scoring as 1-4. The observed protein expression levels and TILs counts were analyzed for correlation to PD-L1 expression, clinicopathological parameters and the responses of PD-1 inhibitors.

      4c3880bb027f159e801041b1021e88e8 Result

      PD-L1 expression was observed in 15 (48%) patients of lung cancer, 8 (26%) of low expression and 7 (23%) of high expression. Positive expression rates of SPOP were 56.3% of negative expression of DP-L1, 50.0% of low expression and 28.6% of high expression. That of CDK4 and CDK6 was 43.8%, 25.0%, 16.6%, and 43.8%, 62.5%, 51.7%, respectively. The positive rate of SPOP (p=0.67), CDK4 (p=0.16) and CDK6 (p=0.37) in PD-L1 positive group was lower than that of PD-L1 negative group, but significant. CD8+ cell count was positive relation to PD-L1 expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data supported previous findings that inhibition of CDK4 and CDK6 increases PD-L1 protein levels and SPOP-deficiency correlated with increased PD-L1 protein abundance.


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