Soo Jung Lee1,2, Sun-Young Jun3, In Hee Lee1,2, Byung Woog Kang1,2, Su Yeon Park4,2, Hye Jin Kim4,2, Jun Seok Park4,2, Gyu-Seog Choi4,2, Ghilsuk Yoon5,6, Jong Gwang Kim7,8. 1. Department of Oncology/Hematology, Kyungpook National University Hospital, Daegu, South Korea. 2. School of Medicine, Kyungpook National University, Daegu, South Korea. 3. Department of Pathology, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, South Korea. 4. Department of Surgery, Kyungpook National University Medical Hospital, Daegu, South Korea. 5. Department of Pathology, Kyungpook National University Hospital, Daegu, South Korea. gsyoon@knu.ac.kr. 6. School of Medicine, Kyungpook National University, Daegu, South Korea. gsyoon@knu.ac.kr. 7. Department of Oncology/Hematology, Kyungpook National University Hospital, Daegu, South Korea. jkk21c@knu.ac.kr. 8. School of Medicine, Kyungpook National University, Daegu, South Korea. jkk21c@knu.ac.kr.
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.
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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