Programmed death-ligand 1 (PD-L1) and immune infiltrates are prognostic for better outcome and enriched in the ATM (ataxia telangiectasia mutated)-low segment of gastric cancer (GC)

Date

08 Oct 2016

Session

Poster Display

Presenters

Elaine Kilgour

Citation

Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371

Authors

E. Kilgour1, H. Angell2, K. Kim3, S. Ahn3, S.T. Kim4, A. Sharpe5, J. Ogden2, A. Davenport6, J.C. Barrett7, D. Hodgson1, J. Lee4

Author affiliations

  • 1 Oncology Translational Science, AstraZeneca, SK10 4TG - Macclesfield/GB
  • 2 Oncology Translational Science, AstraZeneca, Cambridge/GB
  • 3 Pathology And Translational Genomics, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 4 Division Of Hematology-oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 5 Discovery Sciences, AstraZeneca, Cambridge/GB
  • 6 South Manchester, University Hospital, Manchester/GB
  • 7 Oncology Translational Science, AstraZeneca, Boston/US
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Resources

Background

In GC an urgent need exists for effective targeted therapies and predictive markers. In a PhII study, low ATM expression in tumour was associated with greater overall survival (OS) benefit in GC patients treated with olaparib/paclitaxel (1). Antibodies targeting the programmed death-1 checkpoint have reported clinical efficacy in GC, with tumour PD-L1 expression and microsatellite instability (MSI) emerging as predictive markers. We have assessed the prognostic significance of PD-L1 and immune infiltrates in GC and their association with the ATM-low segment.

Methods

PD-L1, CD3+ T-lymphocytes, CD8+ cytotoxic T-cells, human epidermal growth factor receptor 2 (HER2) and ATM expression were assessed by immunohistochemistry (IHC) in a cohort of 384 Korean gastric cancers.

Results

PD-L1 positivity (>0%) on tumour cells (TC) and immune infiltrates (IC) was 16% and 90% respectively and a correlation was observed with MSI (p 

Conclusions

In GC PD-L1, CD3/CD8 are prognostic for better outcome. Mutually exclusive ATM-low and HER2-high segments differ in their immune profile, with the “immunologically hot” ATM-low segment enriched for MSI, PD-L1 and CD3/8. This illustrates the opportunity to employ different strategies for maximising the benefit from immune therapies in HER2 vs ATM segments. (1) Bang et al, (2015) JCO 33:3858-3865

Clinical trial identification

Legal entity responsible for the study

AstraZeneca and Samsung Medical Center

Funding

AstraZeneca

Disclosure

E. Kilgour, H. Angell: Employee and holds stock in AstraZeneca

A. Sharpe, J. Ogden, J.C. Barrett, D. Hodgson: AstraZeneca employee and stockholder

All other authors have declared no conflicts of interest.

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