Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression
PD-L1-mediated immune escape plays an important role in cancer development and progression. Targeting PD-L1 is consider to be an attractive approach for cancer treatment. PD-L1 is a heavily N-linked glycosylated protein, and the glycosylation of PD-L1 is essential for its ability to interact with it...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223018760 |
| _version_ | 1797364203588157440 |
|---|---|
| author | Zhenou Sun Xuan Ma Chong Zhao Lihong Fan Shutao Yin Hongbo Hu |
| author_facet | Zhenou Sun Xuan Ma Chong Zhao Lihong Fan Shutao Yin Hongbo Hu |
| author_sort | Zhenou Sun |
| collection | DOAJ |
| description | PD-L1-mediated immune escape plays an important role in cancer development and progression. Targeting PD-L1 is consider to be an attractive approach for cancer treatment. PD-L1 is a heavily N-linked glycosylated protein, and the glycosylation of PD-L1 is essential for its ability to interact with its receptor PD-1 to mediate immune suppression. In the present study, we demonstrated for the first time that delta-tocotrienol (δ-T3) not any of the other forms of vitamin E was able to disrupt PD-L1 glycosylation mechanistically associated with the suppression of TCF4-STT3a/STT3b axis. The inhibition of PD-L1 glycosylation by δ-T3 resulted in the decrease of PD-L1 expression and its exosomal secretion, leading to the reduction of PD-L1 and PD-1 interaction, and reversing PD-L1-mediated immune suppression, which in turn contributed to the inhibitory effect on tumor growth. The findings of the present study provide a novel mechanistic interpretation for the superior anticancer activity of δ-T3 among 8 isomers of the vitamin E. |
| first_indexed | 2024-03-08T16:32:54Z |
| format | Article |
| id | doaj.art-0d870d99cd9e4610aac7248074157399 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-08T16:32:54Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-0d870d99cd9e4610aac72480741573992024-01-06T04:38:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-01-01170116078Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppressionZhenou Sun0Xuan Ma1Chong Zhao2Lihong Fan3Shutao Yin4Hongbo Hu5College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China; College of Food Science and Nutritional Engineering, Tianjin University of Science and Technology, Tianjin, ChinaCollege of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China; College of Biochemical Engineering, Beijing Union University, Beijing, ChinaCollege of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, ChinaCollege of Veterinary Medicine, China Agricultural University, Beijing, ChinaCollege of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China; Corresponding authors.College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China; Corresponding authors.PD-L1-mediated immune escape plays an important role in cancer development and progression. Targeting PD-L1 is consider to be an attractive approach for cancer treatment. PD-L1 is a heavily N-linked glycosylated protein, and the glycosylation of PD-L1 is essential for its ability to interact with its receptor PD-1 to mediate immune suppression. In the present study, we demonstrated for the first time that delta-tocotrienol (δ-T3) not any of the other forms of vitamin E was able to disrupt PD-L1 glycosylation mechanistically associated with the suppression of TCF4-STT3a/STT3b axis. The inhibition of PD-L1 glycosylation by δ-T3 resulted in the decrease of PD-L1 expression and its exosomal secretion, leading to the reduction of PD-L1 and PD-1 interaction, and reversing PD-L1-mediated immune suppression, which in turn contributed to the inhibitory effect on tumor growth. The findings of the present study provide a novel mechanistic interpretation for the superior anticancer activity of δ-T3 among 8 isomers of the vitamin E.http://www.sciencedirect.com/science/article/pii/S0753332223018760Vitamin Eδ-tocotrienolPD-L1GlycosylationImmune suppression |
| spellingShingle | Zhenou Sun Xuan Ma Chong Zhao Lihong Fan Shutao Yin Hongbo Hu Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression Biomedicine & Pharmacotherapy Vitamin E δ-tocotrienol PD-L1 Glycosylation Immune suppression |
| title | Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression |
| title_full | Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression |
| title_fullStr | Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression |
| title_full_unstemmed | Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression |
| title_short | Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression |
| title_sort | delta tocotrienol disrupts pd l1 glycosylation and reverses pd l1 mediated immune suppression |
| topic | Vitamin E δ-tocotrienol PD-L1 Glycosylation Immune suppression |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223018760 |
| work_keys_str_mv | AT zhenousun deltatocotrienoldisruptspdl1glycosylationandreversespdl1mediatedimmunesuppression AT xuanma deltatocotrienoldisruptspdl1glycosylationandreversespdl1mediatedimmunesuppression AT chongzhao deltatocotrienoldisruptspdl1glycosylationandreversespdl1mediatedimmunesuppression AT lihongfan deltatocotrienoldisruptspdl1glycosylationandreversespdl1mediatedimmunesuppression AT shutaoyin deltatocotrienoldisruptspdl1glycosylationandreversespdl1mediatedimmunesuppression AT hongbohu deltatocotrienoldisruptspdl1glycosylationandreversespdl1mediatedimmunesuppression |