间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题，原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤内 Foxp3(+)RORγt(+) T 细胞浸润决定胃癌患者的不良预后和免疫逃逸微环境
英文原题：Intratumoral Foxp3(+)RORγt(+) T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients.
查看英文原题
Intratumoral Foxp3(+)RORγt(+) T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients.
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研究概要
我们发现 Foxp3 + RORγt + T 细胞可能削弱 CD8 + T 细胞的有效功能，并导致不良的生存结局和较差的化疗反应性。此外，这种新型联合评估系统可能有助于胃癌的预后预测，以指导合适的治疗。新颖性与影响声明：Foxp3 + RORγt + T 细胞在胃癌中的临床意义尚未被研究。在此，我们在 452 例患者中研究了 Foxp3+RORγt+ T 细胞的预后价值。我们证明，瘤内 Foxp3 + RORγt + T 细胞浸润是总生存期的预后生物标志物，并且可识别可能从胃切除术后 5-氟尿嘧啶治疗中获益的患者。
研究思路结论见上方概要
背景
Foxp3 + RORγt + T细胞兼具调节性T细胞和辅助性T细胞17的特征，在自身免疫性疾病中显示出显著的免疫调节功能。然而，Foxp3 + RORγt + T细胞在胃癌中的作用及临床意义尚不清楚。
方法
我们纳入了来自中山医院的452例胃癌组织芯片样本和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了Foxp3 + RORγt + T细胞的浸润情况及免疫微环境。通过Kaplan-Meier曲线、log-rank检验和Cox比例风险模型对患者亚组进行了生存分析。
结果
Foxp3 + RORγt + T 细胞高浸润预示胃癌患者总生存期较差（P = 0.0222 和 0.0110）和治疗反应不佳（交互作用 P = 0.003）。Foxp3 + RORγt + T 细胞与 CD8 + T 细胞有效功能受损相关，表现为干扰素-γ、颗粒酶 B 和 CD107a 表达降低。联合评估 Foxp3 + RORγt + T 细胞和 CD8 + T 细胞可更精确地预测生存结局和化疗反应性。
展开英文摘要原文
BACKGROUND
Foxp3 + RORγt + 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 Foxp3 + RORγt + T cells in gastric cancer remains unclear.
METHODS
We enrolled 452 gastric cancer tissue microarray samples and 60 fresh tumor tissue samples from Zhongshan Hospital. The infiltration of Foxp3 + RORγt + 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.
RESULTS
High infiltration of Foxp3 + RORγt + T cells predicted poor overall survival (P = 0.0222 and 0.0110) and inferior therapeutic response (P = 0.003 for interaction) in gastric cancer. Foxp3 + RORγt + 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 Foxp3 + RORγt + T cells and CD8 + T cells could predict survival outcomes and chemotherapeutic responsiveness more precisely.
CONCLUSIONS
We found that Foxp3 + RORγt + 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. NOVELTY AND IMPACT STATEMENTS: Clinical significance of Foxp3 + RORγts + 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 Foxp3 + RORγt + 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.
论文信息
- 作者
- Fei Y、Cao Y、Gu Y、Fang H、Chen Y、Wang J、Liu X、Lv K
- 第一作者单位
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.China
- 通讯作者单位
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. weijuanzhang@fudan.edu.cn.China
- 期刊
- Cancer immunology, immunotherapy : CII2022 Jan
- 原文标识
- PubMed 33978826 · DOI 10.1007/s00262-021-02950-3
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