Jin Won Kim1, Kyung Han Nam2,3, Sang-Hoon Ahn4, Do Joong Park4, Hyung-Ho Kim4, Se Hyun Kim1, Hyun Chang5, Jeong-Ok Lee1, Yu Jung Kim1, Hye Seung Lee2, Jee Hyun Kim1, Soo-Mee Bang1, Jong Seok Lee1, Keun-Wook Lee6. 1. Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. 2. Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. 3. Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea. 4. Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. 5. Department of Hematology and Medical Oncology, International St. Mary's Hospital, Incheon, Republic of Korea. 6. Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. hmodoctor@snubh.org.
Abstract
BACKGROUND: There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). METHODS: In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(+), CD4(+), CD8(+), or PD-1(+) cells] within the tumor microenvironment were measured using immunohistochemical analysis. RESULTS: Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7% of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (P < 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(+) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9%; 5-year OS rate, 83.0 vs. 69.1% (P values <0.05)]. Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells [5-year DFS rate, 80.9 vs. 67.0%; 5-year OS rate, 82.5 vs. 68.0% (P values <0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables. CONCLUSIONS: GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.
BACKGROUND: There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). METHODS: In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(+), CD4(+), CD8(+), or PD-1(+) cells] within the tumor microenvironment were measured using immunohistochemical analysis. RESULTS: Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7% of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (P < 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(+) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9%; 5-year OS rate, 83.0 vs. 69.1% (P values <0.05)]. Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells [5-year DFS rate, 80.9 vs. 67.0%; 5-year OS rate, 82.5 vs. 68.0% (P values <0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables. CONCLUSIONS: GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3tumor microenvironment are favorable prognostic markers in GC.
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