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Co-inhibition of TIGIT, PD1, and Tim3 reverses dysfunction of Wilms tumor protein-1 (WT1)-specific CD8+T lymphocytes after dendritic cell vaccination in gastric cancer

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机构: [1]Department of Oncology, Beijing Biohealthcare Biotechnology Co., Ltd, China [2]Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, China [3]Key Laboratory of Digestive System Tumors, Second Hospital of Lanzhou University, China [4]Department of Oncology, Beijing Anzhen Hospital Affiliated to The Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, China [5]Department of Biotherapy Center, Gansu Provincial Hospital, China [6]Department of Hemotology, Gansu Provincial Hospital, China [7]Department of Biochemistry and Molecular Biology, Hainan Medical College, China [8]Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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关键词: TIGIT PD1 Tim3 gastric cancer Wilms tumor antigen DC vaccination

摘要:
Dendritic cell (DC) vaccines have been shown to stimulate tumor antigen-specific CD8+ T cells; however, this strategy has demonstrated variable clinical efficacy likely due to immune escape mechanisms that can induce tumor-specific CD8+ T cell dysfunction. Herein, we evaluated the functional characteristics of DC vaccine-induced CD8+ T cells with regard to immune checkpoint inhibitors in gastric cancer patients who were administered Wilms tumor protein-1 (WT1)-targeted DC vaccine. We observed the upregulation of the inhibitory molecule, TIGIT and the inhibitory T cell co-receptors PD1 and Tim3 in limiting WT1-specific CD8+ T cell growth and function in GC patients. TIGIT-expressing PD1+Tim3- CD8+ T cells were the largest subset, while TIGIT+PD1+Tim3+ was the most dysfunctional subset of WT1-specific CD8+ T cells in gastric cancer patients. Importantly, the co-inhibition of TIGIT, PD1, and Tim3 pathways enhanced the growth, proliferation, and cytokine production of WT1-specific CD8+ T cells. In conclusion, our data suggests that targeting TIGIT, PD1, and Tim3 pathways may be important in reversing immune escape in patients with advanced gastric cancer.

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出版当年[2017]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
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出版当年[2016]版:
Q2 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者机构: [1]Department of Oncology, Beijing Biohealthcare Biotechnology Co., Ltd, China
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通讯作者:
通讯机构: [8]Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [*1]Department of Oncology, National Cancer Center/National Cli- nical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Pek- ing Union Medical College, No. 17 South Lane, Pan- jiayuan, Chaoyang District, Beijing 100021, China.
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