Prevalence of PD‑L1 expression is associated with EMAST, density of peritumoral T‑cells and recurrence‑free survival in operable non‑metastatic colorectal cancer
Watson, Martin Matthew Christian; Lea, Dordi; Gudlaugsson, Einar; Skaland, Ivar; Hagland, Hanne Røland; Søreide, Kjetil
Peer reviewed, Journal article
Published version
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Date
2020-08Metadata
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Original version
Watson, M.M., Lea, D., Gudlaugsson, E. et al. (2020) Cancer Immunology and Immunotherapy, 69(8), 1627-1637. 10.1007/s0026 2-020-02573 -0)Abstract
Introduction
Microsatellite instability (MSI) predict response to anti-PD1 immunotherapy in colorectal cancer (CRC). CRCs with MSI have higher infiltration of immune cells related to a better survival. Elevated Microsatellite Alterations at Tetranucleotides (EMAST) is a form of MSI but its association with PD-L1 expression and immune-cell infiltration is not known.
Methods
A consecutive, observational cohort of patients undergoing surgery for CRC. EMAST and clinicopathological characteristics were investigated against PD-L1, as well as CD3 and CD8 expression in the invasive margin or tumour centre (Immunoscore). Difference in survival between groups was assessed by log rank test.
Results
A total of 149 stage I–III CRCs patients, with a median follow up of 60.1 months. Patients with PD-L1+ tumours (7%) were older (median 79 vs 71 years, p = 0.045) and had EMAST+ cancers (OR 10.7, 95% CI 2.2–51.4, p = 0.001). Recurrence-free survival was longer in cancers with PD-L1+ immune cells (HR 0.35, 95% CI 0.16–0.76, p = 0.008, independent of EMAST) and high Immunoscore (HR 0.10, 95% CI 0.01–0.72, p = 0.022). Patients expressing PD-L1 in immune cells had longer disease-specific survival (HR 0.28, 95% CI 0.10–0.77, p = 0.014).
Conclusions
Higher Immunoscore (CD3/CD8 cells) and expression of tumour PD-L1 is found in CRCs with EMAST. Lymphocytic infiltrate and peritumoral PD-L1 expression have prognostic value in CRC.