Abstract
Purpose
This study attempted to reveal the prognostic impact of microsatellite instability-high (MSI-H) colon cancer with tumor-infiltrating immune cells (TIICs) and immune checkpoint protein expression, which are good candidates for immunotherapy.
Materials and methods
The study included 89 patients with MSI-H colon cancer who underwent curative surgery at Kyungpook National University Chilgok Hospital. The expression status of specific inhibitory receptors, such as CD274 (programmed death-ligand 1, PD-L1), PDCD1 (programmed cell death 1, PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and indolamine 2′3′-dioxygenase 1 (IDO1), was retrospectively analyzed using immunohistochemistry (IHC).
Results
Among the 89 patients, CD274, LAG3, and IDO1 expressions in TIICs were observed in 68.6% (61 cases), 13.5% (12), and 28.1% (25) of patients, respectively. Meanwhile, CD274, CTLA4, and IDO1 were expressed in tumor cells of 24.7% (22 cases), 4.5% (4), and 72.0% (64) of patients, respectively. During the median follow-up duration of 39 months, 14 (15.7%) patients experienced disease recurrence. Among the five immune checkpoint proteins, CD274, LAG3, and IDO1 expressions in TIICs were significantly associated with a better disease-free survival (DFS) in a univariate analysis (P = 0.028, 0.037, and 0.030 respectively). Moreover, co-expression of CD274, LAG3, and IDO1 in TIICs showed an even better survival for DFS (P = 0.010). In a multivariate survival analysis, CD274, LAG3, and IDO1 expressions in TIICs remained as independent prognostic factors for a better DFS.
Conclusion
CD274, LAG3, and IDO1 expressions in TIICs showed a better prognosis for patients with MSI-H colon cancer. Thus, the potential therapeutic implications of these immune checkpoint molecules should be further investigated.
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Funding
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (2014R1A5A2009242).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Kyungpook National University Hospital Institutional Review Board (IRB).
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Informed consent was obtained from all individual participants included in the study.
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432_2018_2620_MOESM1_ESM.tif
Supplementary material 1 Supplementary Fig.1. Kaplan–Meier survival curves for disease-free survival according to the immune checkpoint proteins, CD274 (PD-L1), CTLA4, and IDO1 expression in tumor cells identified. (a) CD274 (T). (b) CTLA4 (T). (c) IDO1 (T). P values were calculated according to log-rank test. (TIF 214 KB)
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Lee, S.J., Jun, SY., Lee, I.H. et al. CD274, LAG3, and IDO1 expressions in tumor-infiltrating immune cells as prognostic biomarker for patients with MSI-high colon cancer. J Cancer Res Clin Oncol 144, 1005–1014 (2018). https://doi.org/10.1007/s00432-018-2620-x
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DOI: https://doi.org/10.1007/s00432-018-2620-x