Proinflammatory S100A8 Induces PD-L1 Expression in Macrophages, Mediating Tumor Immune Escape.
J Immunol
; 204(9): 2589-2599, 2020 05 01.
Article
in En
| MEDLINE
| ID: mdl-32198140
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Escape
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Calgranulin A
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B7-H1 Antigen
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Inflammation
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Macrophages
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Neoplasms
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
J Immunol
Year:
2020
Document type:
Article
Affiliation country: