Abstract
IntroductionMicrosatellite 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.MethodsA 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.ResultsA 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).ConclusionsHigher 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.
Highlights
Microsatellite instability (MSI) predict response to anti-PD1 immunotherapy in colorectal cancer (CRC)
We found that patients with Elevated Microsatellite Alterations at Tetranucleotides (EMAST)+ were older, frailer and less likely to have recurrence from CRC [6]
CRC having EMAST correlated with a higher count of intra- and peritumoral CD3+ and CD8+ T-cells and a higher Immunoscore compared to CRC cancers with no EMAST
Summary
Microsatellite instability (MSI) predict response to anti-PD1 immunotherapy in colorectal cancer (CRC). 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. 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. Cancer Immunology, Immunotherapy (2020) 69:1627–1637 downregulation of MSH3, a member of MMR implicated with repair of long indels [4] This proposed mechanism has not been confirmed across patient series, with a previous study from our group refuting an association between MSH3 and EMAST [5]. We found that patients with EMAST+ were older, frailer and less likely to have recurrence from CRC [6]
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