Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Cancer Immunol Immunother. 2022 Jan;71(1):1-11. doi: 10.1007/s00262-021-02950-3. Epub 2021 May 12.
Foxp3RORγt T cells possess both characteristics of regulatory T cells and T helper 17 cells and show significant immunoregulatory functions in autoimmune diseases. However, the role and clinical significance of Foxp3RORγt T cells in gastric cancer remains unclear.
We enrolled 452 gastric cancer tissue microarray samples and 60 fresh tumor tissue samples from Zhongshan Hospital. The infiltration of Foxp3RORγt T cells and immune contexture were examined by immunohistochemistry and flow cytometry. Survival analyses of patient subgroups were conducted by Kaplan-Meier curves, log-rank test and Cox proportional model.
High infiltration of Foxp3RORγt T cells predicted poor overall survival (P = 0.0222 and 0.0110) and inferior therapeutic response (P = 0.003 for interaction) in gastric cancer. Foxp3RORγt T cells were associated with impaired effective function of CD8 T cells featured by decreased interferon-γ, granzyme B and CD107a expression. Co-evaluation of Foxp3RORγt T cells and CD8 T cells could predict survival outcomes and chemotherapeutic responsiveness more precisely.
We found that Foxp3RORγt T cells could potentially attenuate effective functions of CD8 T cells and led to adverse survival outcomes and inferior chemotherapeutic responsiveness. Moreover, the novel co-evaluation system might be useful for prognosis prediction for appropriate treatment in gastric cancer.
Clinical significance of Foxp3RORγts T cells has not been studied in gastric cancer. Herein, we investigated the prognostic value of Foxp3+RORγt+ T cells in 452 patients. We demonstrated that intratumoral Foxp3RORγt T cell infiltration was a prognostic biomarker for overall survival and the identification of patients might benefit from post-gastrectomy 5-fluorouracil. These findings allow a more precise stratification upon the co-evaluation with CD8 T cells to better clinical management for patients who would benefit from 5-fluorouracil.
Foxp3RORγt T 细胞兼具调节性 T 细胞和辅助性 T 细胞 17 的特征，并在自身免疫性疾病中表现出显著的免疫调节功能。然而，Foxp3RORγt T 细胞在胃癌中的作用和临床意义尚不清楚。
我们纳入了来自中山医院的 452 例胃癌组织微阵列样本和 60 例新鲜肿瘤组织样本。通过免疫组织化学和流式细胞术检测 Foxp3RORγt T 细胞的浸润和免疫微环境。通过 Kaplan-Meier 曲线、log-rank 检验和 Cox 比例模型对患者亚组的生存情况进行分析。
Foxp3RORγt T 细胞的高浸润预示着胃癌患者的总生存期较差（P=0.0222 和 0.0110）和治疗反应不良（交互作用 P=0.003）。Foxp3RORγt T 细胞与 CD8 T 细胞有效功能受损有关，表现为干扰素-γ、颗粒酶 B 和 CD107a 表达降低。Foxp3RORγt T 细胞与 CD8 T 细胞的联合评估可以更准确地预测生存结局和化疗反应性。
我们发现 Foxp3RORγt T 细胞可能削弱 CD8 T 细胞的有效功能，导致不良的生存结局和化疗反应不良。此外，新型的联合评估系统可能有助于预测胃癌患者的预后，并为其提供适当的治疗。
Foxp3RORγts T 细胞在胃癌中的临床意义尚未得到研究。在此，我们研究了 Foxp3+RORγt+T 细胞在 452 例患者中的预后价值。我们发现肿瘤内 Foxp3RORγt T 细胞浸润是总生存期的预后生物标志物，对这些患者的识别可能有益于氟尿嘧啶化疗后的胃切除术。这些发现使得在与 CD8 T 细胞联合评估时可以更精确地分层，以便更好地为受益于氟尿嘧啶治疗的患者进行临床管理。
