Department of Radiotherapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Cancer Med. 2019 Dec;8(17):7330-7344. doi: 10.1002/cam4.2596. Epub 2019 Oct 20.
BACKGROUND: The tumor microenvironment represents an abnormal niche containing numerous factors, such as T cells, dendritic cells (DCs), regulatory T cells (Tregs), and indoleamine 2,3-dioxygenase (IDO), involved in maintaining immune homeostasis and tolerance. All these factors may influence the choice of therapy and the clinical outcomes. METHODS: Flow cytometry was performed to identify CD4+/CD8 + T cells and DCs, and immunohistochemistry was used to evaluate IDO and Forkhead Box P3 (Foxp3) expression; these experiments were performed in order to explore the clinical and prognostic significance of CD4/CD8 + T cells, DCs, Tregs, and IDO expression in gastric carcinoma. RESULTS: Smaller tumor size was correlated with higher expression levels of peripheral CD4 + T cells (P = .003) and CD8 + T cells (P = .002), and lower IDO expression (P = .044) in tumors. Well-differentiated gastric carcinomas displayed higher peripheral (P = .029) and tumor-infiltrating CD4 + T cell (P = .009) populations and a higher tumor-infiltrating DC1/DC2 ratio (P = .048). Gastric cancer in the early T stages exhibited higher populations of peripheral DC2s (P = .044) and a higher tumor-infiltrating DC1/DC2 ratio (P = .012). Gastric cancer at the N0 stage had lower tumor-infiltrating DC2s (P = .032) and a higher DC1/DC2 ratio (P = .037). IDO expression was positively correlated with tumor-infiltrating Foxp3 + Tregs (P < .001) as well as DC2s (P < .001), whereas it was negatively correlated with the tumor-infiltrating CD4/CD8 + T cell ratio (P = .023). Tumor-infiltrating Foxp3 + Treg was positively correlated with tumor-infiltrating DC2s (r = 0.772; P < .001). At T, N, and TNM stages, the expression levels of peripheral DC2s, tumor-infiltrating DC1/DC2 ratios, Foxp3 + Tregs, and IDO were significantly correlated with prognosis (P < .05). The T stage and peripheral DC2s were significant risk factors for overall survival. CONCLUSION: Immunocompetent cells and humoral immune factors, including DC2s, CD4+/CD8 + T cells, Foxp3 + Tregs, and IDO, interact with each other to compose a complex community of tumor immune microenvironment, ultimately affecting tumor progression and survival of gastric cancer.
背景：肿瘤微环境代表了一个包含众多因素的异常生态位，如 T 细胞、树突状细胞（DCs）、调节性 T 细胞（Tregs）和吲哚胺 2,3-双加氧酶（IDO），这些因素共同参与维持免疫稳态和耐受。所有这些因素都可能影响治疗选择和临床结果。
方法：采用流式细胞术鉴定 CD4+/CD8+T 细胞和 DCs，免疫组织化学法检测 IDO 和叉头框 P3（Foxp3）的表达，探讨 CD4/CD8+T 细胞、DCs、Tregs 和 IDO 表达在胃癌中的临床和预后意义。
结果：肿瘤较小者外周血 CD4+T 细胞（P=.003）和 CD8+T 细胞（P=.002）表达较高，肿瘤中 IDO 表达较低（P=.044）。分化较好的胃癌患者外周（P=.029）和肿瘤浸润 CD4+T 细胞（P=.009）以及肿瘤浸润 DC1/DC2 比值较高（P=.048）。早期 T 期胃癌患者外周 DC2 细胞（P=.044）和肿瘤浸润 DC1/DC2 比值较高（P=.012）。N0 期胃癌患者肿瘤浸润 DC2 细胞（P=.032）和 DC1/DC2 比值较高（P=.037）。IDO 表达与肿瘤浸润 Foxp3+Tregs（P<.001）以及 DC2s（P<.001）呈正相关，与肿瘤浸润 CD4/CD8+T 细胞比值呈负相关（P=.023）。肿瘤浸润 Foxp3+Treg 与肿瘤浸润 DC2 呈正相关（r=0.772；P<.001）。在 T、N 和 TNM 分期中，外周 DC2 细胞、肿瘤浸润 DC1/DC2 比值、Foxp3+Tregs 和 IDO 的表达与预后显著相关（P<.05）。T 期和外周 DC2 细胞是总生存的显著危险因素。
结论：包括 DC2、CD4+/CD8+T 细胞、Foxp3+Tregs 和 IDO 在内的免疫细胞和体液免疫因子相互作用，构成了一个复杂的肿瘤免疫微环境共同体，最终影响胃癌的肿瘤进展和生存。
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