Abstract 3221
Background
Neoadjuvant and/or adjuvant treatment has led to an improved survival in patients with resectable gastroesophageal adenocarcinoma (GEAC). Nevertheless, survival rates remain poor and, hence, there is a great need to identify novel treatment strategies and relevant complementary diagnostics. Immunotherapies targeting the PD‐1/PD‐L1 checkpoints have shown promising results, but simultaneous inhibition of other fundamental checkpoints, such as lymphocyte-activation gene-3 (LAG‐3), may further improve clinical outcome. The expression and prognostic significance of LAG-3 in GEAC has however not yet been described. Herein, we examined the expression of LAG-3 in tumour-infiltrating immune cells (TIC) in chemoradiotherapy-naïve GEAC and paired lymph node metastases, with particular reference to its relationship with PD-1 and PD-L1 expression, mismatch repair (MMR) status, and survival.
Methods
Immunohistochemical LAG-3 expression was analysed in tissue microarrays with 165 primary tumours and 72 paired lymph node metastases from a retrospective consecutive cohort of patients with chemoradiotherapy-naïve resected GEAC. LAG-3 expression was denoted in categories of negative (0), low (1-10) and high (>10). PD-1, PD-L1 expression and MMR status had been previously analysed.
Results
The distribution of LAG-3 expression in primary tumours was 55.8% negative, 28.5% low, and 15.8% high. The corresponding figures in lymph node metastases were 48.6% negative, 37.5% low, and 13.9% high. LAG-3 expression did not differ by tumour location. Positive LAG-3 expression in primary tumours was an independent factor for prolonged overall survival in the entire cohort (HR = 0.64, 95% CI 0.43-0.96), and in gastric cancer (HR = 0.35, 95% CI 0.17-0.74). LAG-3 expression in primary tumours was significantly associated with PD-L1 expression in both tumour cells and TIC, and with PD-1 expression in TIC, but not with MMR status.
Conclusions
LAG-3 is expressed in a considerable proportion of GEAC, with a similar distribution in primary tumours and lymph node metastases. Positive LAG-3 expression is an independent favourable prognostic factor, particularly in gastric cancer.
Clinical trial identification
Legal entity responsible for the study
Lund University.
Funding
The Swedish Research Council, The Swedish Cancer Society, University Hospital Research Grant, Mrs Berta Kamprad Foundation, Swedish Government Grant for Clinical research (ALF).
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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