Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway
Abstract Background Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. Results The r...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-024-01876-3 |
| _version_ | 1797199172028334080 |
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| author | Yunwen Zhang Yao Lei Qian Ou Mengdie Chen Sicheng Tian Jing Tang Ruidan Li Qian Liang Zhaobin Chen Chuan Wang |
| author_facet | Yunwen Zhang Yao Lei Qian Ou Mengdie Chen Sicheng Tian Jing Tang Ruidan Li Qian Liang Zhaobin Chen Chuan Wang |
| author_sort | Yunwen Zhang |
| collection | DOAJ |
| description | Abstract Background Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. Results The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs. Conclusions Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression. |
| first_indexed | 2024-04-24T07:11:31Z |
| format | Article |
| id | doaj.art-1d1a1a4ca2434224bdb9cd7c86637a8c |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-24T07:11:31Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-1d1a1a4ca2434224bdb9cd7c86637a8c2024-04-21T11:30:33ZengBMCBMC Biology1741-70072024-04-0122111710.1186/s12915-024-01876-3Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathwayYunwen Zhang0Yao Lei1Qian Ou2Mengdie Chen3Sicheng Tian4Jing Tang5Ruidan Li6Qian Liang7Zhaobin Chen8Chuan Wang9West China School of Public Health and West China Fourth Hospital, Sichuan UniversityWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityShen Zhen Biomed Alliance Biotech Group Co., LtdWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityShen Zhen Biomed Alliance Biotech Group Co., LtdWest China School of Public Health and West China Fourth Hospital, Sichuan UniversityAbstract Background Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. Results The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs. Conclusions Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression.https://doi.org/10.1186/s12915-024-01876-3Listeria-vectored tumor vaccinesCervical cancerImmunosuppressionMDSCsJAK-STAT |
| spellingShingle | Yunwen Zhang Yao Lei Qian Ou Mengdie Chen Sicheng Tian Jing Tang Ruidan Li Qian Liang Zhaobin Chen Chuan Wang Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway BMC Biology Listeria-vectored tumor vaccines Cervical cancer Immunosuppression MDSCs JAK-STAT |
| title | Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway |
| title_full | Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway |
| title_fullStr | Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway |
| title_full_unstemmed | Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway |
| title_short | Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway |
| title_sort | listeria vectored cervical cancer vaccine candidate strains reduce mdscs via the jak stat signaling pathway |
| topic | Listeria-vectored tumor vaccines Cervical cancer Immunosuppression MDSCs JAK-STAT |
| url | https://doi.org/10.1186/s12915-024-01876-3 |
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