PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells
Abstract Background PRDX2 is significantly expressed in various cancers and is associated with the proliferation of tumor cells. Nonetheless, the precise mechanism of PRDX2 in tumor immunity remains incompletely understood. This study aims to investigate the impact of PRDX2, which is highly expresse...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05888-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594520943886336 |
|---|---|
| author | Yunjia Dong Anqi Cheng Jiawei Zhou Jianqiang Guo Yafeng Liu Xuan Li Maoqian Chen Dong Hu Jing Wu |
| author_facet | Yunjia Dong Anqi Cheng Jiawei Zhou Jianqiang Guo Yafeng Liu Xuan Li Maoqian Chen Dong Hu Jing Wu |
| author_sort | Yunjia Dong |
| collection | DOAJ |
| description | Abstract Background PRDX2 is significantly expressed in various cancers and is associated with the proliferation of tumor cells. Nonetheless, the precise mechanism of PRDX2 in tumor immunity remains incompletely understood. This study aims to investigate the impact of PRDX2, which is highly expressed in lung adenocarcinoma, on T cells in the tumor immune microenvironment, and its immune action target to promote the immune escape of lung cancer cells, to provide a theoretical basis for lung adenocarcinoma treatment with PRDX2 as the target. Methods Mouse animal models to verify the effect of Conoidin A treatment on tumor growth and T cell infiltration. Flow cytometry and Western blot verified tumor cell apoptosis in the in vitro co-culture system as well as granzyme B and perforin expression in T cells. RNA-Seq was used to obtain the downstream immune molecule. si-RNA knockdown of Galectin-9 was co-cultured with T cells in vitro. Immunofluorescence and Western blot verified that PRDX2 regulates Galectin-9 expression through HDAC3. Results PRDX2 expression was negatively correlated with CD8+ T cell expression in LUAD patients. Inhibition of PRDX2 significantly enhanced T-cell killing of LUAD cells and reduced tumor load in both in vitro and in vivo models. Mechanistically, Conoidin A or shRNA_PRDX2 decreased Galectin-9 expression by down-regulating the phosphorylation of HDAC3, consequently enhancing the infiltration and function of CD8+ T cells. Conclusions This study reveals the role of the PRDX2/HDAC3/Galectin-9 axis in LUAD immune escape and indicates Galectin-9 as a promising target for immunotherapy. |
| format | Article |
| id | doaj-art-f194c6421ad1418680679b9690cead33 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-f194c6421ad1418680679b9690cead332025-01-19T12:37:24ZengBMCJournal of Translational Medicine1479-58762025-01-0123111610.1186/s12967-024-05888-zPRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cellsYunjia Dong0Anqi Cheng1Jiawei Zhou2Jianqiang Guo3Yafeng Liu4Xuan Li5Maoqian Chen6Dong Hu7Jing Wu8School of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologySchool of Medicine, Anhui University of Science and TechnologyThe First Affiliated Hospital of Anhui University of Science and Technology (Huainan First People’s Hospital, School of Medicine)Joint Research Center for Occupational Medicine and Health of IHM, School of Medicine, Anhui University of Science and TechnologyAbstract Background PRDX2 is significantly expressed in various cancers and is associated with the proliferation of tumor cells. Nonetheless, the precise mechanism of PRDX2 in tumor immunity remains incompletely understood. This study aims to investigate the impact of PRDX2, which is highly expressed in lung adenocarcinoma, on T cells in the tumor immune microenvironment, and its immune action target to promote the immune escape of lung cancer cells, to provide a theoretical basis for lung adenocarcinoma treatment with PRDX2 as the target. Methods Mouse animal models to verify the effect of Conoidin A treatment on tumor growth and T cell infiltration. Flow cytometry and Western blot verified tumor cell apoptosis in the in vitro co-culture system as well as granzyme B and perforin expression in T cells. RNA-Seq was used to obtain the downstream immune molecule. si-RNA knockdown of Galectin-9 was co-cultured with T cells in vitro. Immunofluorescence and Western blot verified that PRDX2 regulates Galectin-9 expression through HDAC3. Results PRDX2 expression was negatively correlated with CD8+ T cell expression in LUAD patients. Inhibition of PRDX2 significantly enhanced T-cell killing of LUAD cells and reduced tumor load in both in vitro and in vivo models. Mechanistically, Conoidin A or shRNA_PRDX2 decreased Galectin-9 expression by down-regulating the phosphorylation of HDAC3, consequently enhancing the infiltration and function of CD8+ T cells. Conclusions This study reveals the role of the PRDX2/HDAC3/Galectin-9 axis in LUAD immune escape and indicates Galectin-9 as a promising target for immunotherapy.https://doi.org/10.1186/s12967-024-05888-zPRDX2Lung adenocarcinomaHDAC3Galectin-9Immune checkpoint |
| spellingShingle | Yunjia Dong Anqi Cheng Jiawei Zhou Jianqiang Guo Yafeng Liu Xuan Li Maoqian Chen Dong Hu Jing Wu PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells Journal of Translational Medicine PRDX2 Lung adenocarcinoma HDAC3 Galectin-9 Immune checkpoint |
| title | PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells |
| title_full | PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells |
| title_fullStr | PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells |
| title_full_unstemmed | PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells |
| title_short | PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells |
| title_sort | prdx2 induces tumor immune evasion by modulating the hdac3 galectin 9 axis in lung adenocarcinoma cells |
| topic | PRDX2 Lung adenocarcinoma HDAC3 Galectin-9 Immune checkpoint |
| url | https://doi.org/10.1186/s12967-024-05888-z |
| work_keys_str_mv | AT yunjiadong prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT anqicheng prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT jiaweizhou prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT jianqiangguo prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT yafengliu prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT xuanli prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT maoqianchen prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT donghu prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells AT jingwu prdx2inducestumorimmuneevasionbymodulatingthehdac3galectin9axisinlungadenocarcinomacells |