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.
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.
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
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
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.