Yuchao Fei1, Yifan Cao2, Yun Gu1, Hanji Fang1, Yifan Chen3, Jieti Wang4, Xin Liu1, Kunpeng Lv1, Xudong He1, Chao Lin2, Hao Liu2, He Li2, Hongyong He2, Ruochen Li5, Heng Zhang6, Weijuan Zhang7. 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. 2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. 3. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. 4. Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 5. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. rcli12@fudan.edu.cn. 6. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. zhang.heng@zs-hospital.sh.cn. 7. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. weijuanzhang@fudan.edu.cn.
Abstract
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.
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.
Authors: J S Macdonald; S R Smalley; J Benedetti; S A Hundahl; N C Estes; G N Stemmermann; D G Haller; J A Ajani; L L Gunderson; J M Jessup; J A Martenson Journal: N Engl J Med Date: 2001-09-06 Impact factor: 91.245
Authors: Charles S Fuchs; Toshihiko Doi; Raymond W Jang; Kei Muro; Taroh Satoh; Manuela Machado; Weijing Sun; Shadia I Jalal; Manish A Shah; Jean-Phillipe Metges; Marcelo Garrido; Talia Golan; Mario Mandala; Zev A Wainberg; Daniel V Catenacci; Atsushi Ohtsu; Kohei Shitara; Ravit Geva; Jonathan Bleeker; Andrew H Ko; Geoffrey Ku; Philip Philip; Peter C Enzinger; Yung-Jue Bang; Diane Levitan; Jiangdian Wang; Minori Rosales; Rita P Dalal; Harry H Yoon Journal: JAMA Oncol Date: 2018-05-10 Impact factor: 31.777
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