Programmed death-ligand 1 (PDL-1) and immune infiltrates are prognostic for better outcome and enriched in the ATM (ataxia telangiectasia mutated)-low segment of gastric cancer (GC)
Session type: Poster / e-Poster / Silent Theatre session
Theme: Diagnosis and therapy
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 patients treated with lynparza/paclitaxel. Antibodies targeting the programmed death-1 checkpoint have reported 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 correlated with MSI (p<0.01) and immune infiltrates (CD3 P<0.05; CD8 P<0.01). PD-L1 TC and CD8 were not associated with Lauren subtype. Multivariate analysis showed PD-L1 TC positivity, CD3 and CD8 significantly associated with better OS (p<0.01) and DFS (disease free survival; p<0.01). Prevalence of HER2-high (IHC 3+) was 7% and ATM-low (<10% TC positive) was 11.5% and were largely mutually exclusive; only 1/27 HER2-high was also ATM-low. The majority (89%) of HER2-high tumours were microsatellite stable (MSS) with a trend for lower prevalence of PD-L1 (7.4 vs 17%) and CD8 (11.5 vs 21%). The ATM-low segment was significantly enriched for PD-L1 (p<0.01), CD8 (p<0.05) and MSI (p<0.01), but heterogenous with 46% ATM-low tumours being MSS and 65% PD-L1 TC negative.
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.