食管鳞癌肿瘤微环境中IL-1β通过STAT3依赖和非依赖方式上调PD-L1机制研究及临床意义

批准号:
81960552
项目类别:
地区科学基金项目
资助金额:
33.0 万元
负责人:
郑树涛
依托单位:
学科分类:
肿瘤免疫治疗
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
郑树涛
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中文摘要
中晚期食管鳞癌的化疗与靶向治疗效果有限、复发率和转移率偏高,致使食管癌患者总体预后较差。因此,探索食管癌治疗新方法迫在眉睫。目前基于PD-1/PD-L1的免疫治疗食管癌方面的研究尚处于起步阶段,而评估肿瘤患者的PD-L1的表达水平是接受抗PD-L1免疫治疗的关键。我们前期发现源于M2型肿瘤相关巨噬细胞的IL-1β能显著性上调食管癌细胞的PD-L1表达,但调控机制尚不明确。基于前期实验,我们假设食管鳞癌微环境中IL-1β通过STAT3依赖和非依赖方式上调PD-L1表达。本项目将从临床组织中扩大样本分析食管癌组织中IL-1β与PD-L1表达的临床相关性及预后判断价值;在细胞和动物模型中深入研究IL-1β在食管癌微环境中调控PD-L1的作用机制,探讨IL-1β在食管鳞癌免疫治疗中是否可作为联合PD-L1抗体的一个肿瘤免疫治疗靶点,从而为食管鳞癌的抗PD-L1免疫治疗提供理论实验依据。
英文摘要
The effect of chemotherapy or target therapy for esophageal squamous cell carcinoma (ESCC) at advanced stage was actually limited, the tumourous recurrent and metastasis always tend to be higher, which eventually contribute to unfavorable overall prognosis. exploration of new therapy for ESCC is therefore urgent. Currently, tumor immunotherapy based on anti-PD-1/PD-L1 in ESCC is still in its infancy, wherein taking stock of PD-L1 expression is the prerequisite for cancer patients whether or not could receive the immunotherapy targeting PD-1/PD-L1. In our previous study, IL-1β derived from M2 tumor-associated macrophages (M2 TAMs) was shown to be able to up-regulate the expression of PD-L1 on ESCC cells, the mechanism through which remains far from unknown. On the basis of our earlier trials together with relevant reports, we hypothesized that IL-1β derived from M2 TAMs could regulate PD-L1 via STAT3-dependent and STAT3–independent in ESCC cells. In the present study, we are going to expand the clinical specimens to analyze the correlation between IL-1β and PD-L1 and analyze the clinicopathological and prognostic significance of IL-1β and PD-L1 in ESCC tissues; meanwhile, we will go on dig up the regulatory molecular mechanism through which IL-1β regulates PD-L1 expression both in vitro ESCC cell lines and in vivo Xenograft mice model, thereby providing the experimental evidence for immunotherapy of ESCC.
期刊论文列表
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科研奖励列表
会议论文列表
专利列表
DOI:--
发表时间:2021
期刊:新疆医科大学学报
影响因子:--
作者:郑树涛;刘清;刘涛;杨丽菲;张琪琪;韩秀娟;阿尔孜古丽·吐尔逊;卢晓梅
通讯作者:卢晓梅
DOI:--
发表时间:2023
期刊:Cell Biol Int.
影响因子:--
作者:He S;Liang Y;Tan Y;Liu Q;Liu T;Lu X;Zheng S
通讯作者:Zheng S
DOI:10.1016/j.bbrc.2020.03.055
发表时间:2020-03
期刊:Biochemical and biophysical research communications
影响因子:3.1
作者:Shutao Zheng;Qing Liu;Tao Liu;Lifei Yang;Qiqi Zhang;Tongxue Shen;Xiao Zhang;Xiujuan Han;Xiaomei Lu
通讯作者:Shutao Zheng;Qing Liu;Tao Liu;Lifei Yang;Qiqi Zhang;Tongxue Shen;Xiao Zhang;Xiujuan Han;Xiaomei Lu
DOI:10.3390/cancers14225532
发表时间:2022-11-10
期刊:CANCERS
影响因子:5.2
作者:Zheng, Shutao;Liang, Yan;Tan, Yiyi;Li, Lu;Liu, Qing;Liu, Tao;Lu, Xiaomei
通讯作者:Lu, Xiaomei
DOI:10.1016/j.heliyon.2023.e14571
发表时间:2023-03
期刊:HELIYON
影响因子:4
作者:Zheng, Shutao;Liu, Tao;Li, Lu;Liu, Qing;Huang, Conggai;Liang, Yan;Tan, Yiyi;Zhang, Li;Lu, Xiaomei
通讯作者:Lu, Xiaomei
PKM2突变相关的PSD3调控PD-L1/L2介导食管鳞癌免疫逃逸的机制研究及临床意义
- 批准号:82360521
- 项目类别:地区科学基金项目
- 资助金额:32万元
- 批准年份:2023
- 负责人:郑树涛
- 依托单位:
KIAA1377在食管癌淋巴结转移中的作用及机制研究
- 批准号:81360357
- 项目类别:地区科学基金项目
- 资助金额:50.0万元
- 批准年份:2013
- 负责人:郑树涛
- 依托单位:
国内基金
海外基金
