例如:"lncRNA", "apoptosis", "WRKY"

Proinflammatory S100A8 Induces PD-L1 Expression in Macrophages, Mediating Tumor Immune Escape.

J Immunol. 2020 May 01;204(9):2589-2599. Epub 2020 Mar 20
Zhengshuo Li 1 , Jing Wang 2 , Xuemei Zhang 3 , Peishan Liu 4 , Xiaoyue Zhang 4 , Jia Wang 4 , Xiang Zheng 4 , Lingyu Wei 4 , Qiu Peng 4 , Can Liu 4 , Qun Yan 5 , Shourong Shen 6 , Xiayu Li 6 , Jian Ma 6
Zhengshuo Li 1 , Jing Wang 2 , Xuemei Zhang 3 , Peishan Liu 4 , Xiaoyue Zhang 4 , Jia Wang 4 , Xiang Zheng 4 , Lingyu Wei 4 , Qiu Peng 4 , Can Liu 4 , Qun Yan 5 , Shourong Shen 6 , Xiayu Li 6 , Jian Ma 6
+ et al

[No authors listed]

Author information
  • 1 NHC Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Central South University, Changsha 410078, China.
  • 2 Department of Gastroenterology, People's Hospital of Shimen County, Shimen, Hunan 415300, China.
  • 3 Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, China; and.
  • 4 Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha 410078, China.
  • 5 Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 6 Department of Gastroenterology, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha 410013, China.

摘要


S100A8 is a damage-associated molecular pattern protein released by monocytes, playing a decisive role in the development of inflammation. Nonresolving inflammation is viewed as a driving force in tumorigenesis, and its role in tumor immune escape also attracted attentions. PD-1/PD-L1 axis is a critical determinant of physiological immune homeostasis, and anti-PD-1 or PD-L1 therapy has becoming the most exciting field of oncology. Multiple regulation mechanisms have been contributed to PD-L1 expression modulation including inflammatory mediators. In this study we reported that S100A8 significantly induced PD-L1 expression in monocytes/macrophages but not in tumor cells. S100A8 induced PD-L1 transcription through the TLR4 receptor and multiple crucial pathways of inflammation process. S100A8 modulated the histone modification of the PD-L1 promoter in monocytes/macrophages. S100A8-pretreated macrophages had immunosuppressive function and attenuated the antitumor ability of CTLs both in vitro and in vivo. A highly positive correlation existed between S100A8 expression and PD-L1 expression in human cancer specimens. To our knowledge, our study uncovers a novel molecular mechanism for regulating PD-L1 transcription by an inflammatory mediator S100A8, and reveals the importance of comprehensive understanding the role of inflammation in tumorigenesis as well as in tumor immune escape.