Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization
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...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-021-00810-2 |
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| author | Yi Yuan Pengfei Jiao Zeyu Wang Mengqi Chen Hongming Du Liang Xu Juanyong Xu Youjin Dai Fu-gen Wu Yaqin Zhang Heming Wu |
| author_facet | Yi Yuan Pengfei Jiao Zeyu Wang Mengqi Chen Hongming Du Liang Xu Juanyong Xu Youjin Dai Fu-gen Wu Yaqin Zhang Heming Wu |
| author_sort | Yi Yuan |
| collection | DOAJ |
| description | 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. Graphical abstract Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization. Video Abstract. |
| first_indexed | 2024-12-13T13:47:06Z |
| format | Article |
| id | doaj.art-868ed24dc86c4bcaa43e09ca0680aaac |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-13T13:47:06Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-868ed24dc86c4bcaa43e09ca0680aaac2022-12-21T23:43:22ZengBMCCell Communication and Signaling1478-811X2022-01-0120111310.1186/s12964-021-00810-2Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarizationYi Yuan0Pengfei Jiao1Zeyu Wang2Mengqi Chen3Hongming Du4Liang Xu5Juanyong Xu6Youjin Dai7Fu-gen Wu8Yaqin Zhang9Heming Wu10Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityKey Laboratory of Model Animal Research, Animal Core Facility of Nanjing Medical University, Nanjing Medical UniversityState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast UniversityKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical UniversityJiangsu Key Laboratory of Oral Diseases, Nanjing Medical UniversityAbstract 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. Graphical abstract Exosomal PD-L1 secreted by ER-stressed OSCC cells promoted M2 macrophage polarization. Video Abstract.https://doi.org/10.1186/s12964-021-00810-2Oral squamous cell carcinomaMacrophageEndoplasmic reticulum stressExosomePD-L1 |
| spellingShingle | Yi Yuan Pengfei Jiao Zeyu Wang Mengqi Chen Hongming Du Liang Xu Juanyong Xu Youjin Dai Fu-gen Wu Yaqin Zhang Heming Wu Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization Cell Communication and Signaling Oral squamous cell carcinoma Macrophage Endoplasmic reticulum stress Exosome PD-L1 |
| title | Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization |
| title_full | Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization |
| title_fullStr | Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization |
| title_full_unstemmed | Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization |
| title_short | Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization |
| title_sort | endoplasmic reticulum stress promotes the release of exosomal pd l1 from head and neck cancer cells and facilitates m2 macrophage polarization |
| topic | Oral squamous cell carcinoma Macrophage Endoplasmic reticulum stress Exosome PD-L1 |
| url | https://doi.org/10.1186/s12964-021-00810-2 |
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