Intratumoral Foxp3 <superscript>+</superscript> RORγt <superscript>+</superscript> T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients. - OpacWWW

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Tytuł:: Intratumoral Foxp3 T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients.
Autorzy:: Fei Y; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Cao Y; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Gu Y; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Fang H; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Chen Y; Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Wang J; Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Liu X; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Lv K; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
He X; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Lin C; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Liu H; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Li H; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
He H; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Li R; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. .
Zhang H; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. .
Zhang W; Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. .
Źródło:: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2022 Jan; Vol. 71 (1), pp. 1-11. Date of Electronic Publication: 2021 May 12.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: Berlin : Springer Verlag
Original Publication: Berlin ; New York, NY : Springer International, c1982-
MeSH Terms:: Gene Expression Regulation, Neoplastic*
Forkhead Transcription Factors/*biosynthesis
Nuclear Receptor Subfamily 1, Group F, Member 3/*biosynthesis
Stomach Neoplasms/*immunology
Stomach Neoplasms/*metabolism
T-Lymphocytes/*cytology
Aged ; Autoimmune Diseases/immunology ; CD8-Positive T-Lymphocytes/cytology ; Chemotherapy, Adjuvant ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphocytes, Tumor-Infiltrating ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Tissue Array Analysis ; Treatment Outcome
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Grant Information:: 81671628 National Natural Science Foundation of China; 81871306 National Natural Science Foundation of China; 81871926 National Natural Science Foundation of China; 81902402 National Natural Science Foundation of China; 81902901 National Natural Science Foundation of China; 81972219 National Natural Science Foundation of China; 18ZR1432900 Shanghai Municipal Natural Science Foundation; 17YF1402200 Shanghai Sailing Program; 18YF1404600 Shanghai Sailing Program; 19YF1407500 Shanghai Sailing Program; 21YF1407600 Shanghai Sailing Program
Contributed Indexing:: Keywords: Adjuvant chemotherapy; Chemotherapeutic responsiveness; Foxp3+RORγt+ T cells; Gastric cancer; Prognosis
Substance Nomenclature:: 0 (FOXP3 protein, human)
0 (Forkhead Transcription Factors)
0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
0 (RORC protein, human)
Entry Date(s):: Date Created: 20210512 Date Completed: 20220117 Latest Revision: 20230415
Update Code:: 20240105
DOI:: 10.1007/s00262-021-02950-3
PMID:: 33978826
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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.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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Intratumoral Foxp3 + RORγt + T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients.