Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization.
Cell Commun Signal
; 20(1): 12, 2022 01 28.
Article
em En
| MEDLINE
| ID: mdl-35090495
ABSTRACT
BACKGROUND:
Endoplasmic reticulum (ER) stress has been found to foster the escape of cancer cells from immune surveillance and upregulate PD-L1 expression. However, the underlying mechanisms are unknown.METHODS:
While analyzing the protein levels using immunofluorescence and Western blotting, the RNA levels were measured using qRT-PCR. Ten injection of exosomes into six-week-old nude mice was made through the tail vein once every other day in total.RESULTS:
The expression of certain ER stress markers such as PERK (PKR-like endoplasmic reticulum kinase), ATF6 (activating transcription factor 6), and GRP78 (glucose-regulated protein 78), was found to be upregulated in the oral squamous cell carcinoma (OSCC) tissues and related to poor overall survival. There is a positive relationship between the extent of ER stress-related proteins and a cluster of PD-L1 expression and macrophage infiltration among the OSCC tissues. Further, incubation with exosomes derived from ER-stressed HN4 cells (Exo-ER) was found to upregulate PD-L1 extents in macrophages in vitro and in vivo, and macrophage polarization toward the M2 subtype was promoted by upregulating PD-L1.CONCLUSIONS:
ER stress causes OSCC cells to secrete exosomal PD-L1 and upregulates PD-L1 expression in macrophages to drive M2 macrophage polarization. The delineation of a new exosome-modulated mechanism was made for OSCC-macrophage crosstalk driving tumor development and to be examined for its therapeutic use. Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization. Video Abstract.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Bucais
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Antígeno B7-H1
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Estresse do Retículo Endoplasmático
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Carcinoma de Células Escamosas de Cabeça e Pescoço
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Neoplasias de Cabeça e Pescoço
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Macrófagos
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article