FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment
Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have e...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2423983 |
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| author | Shan Wang Shasha Jiang Xu Li Huan Huang Xu Qiu Meng Yu Xiaoli Yang Fengjun Liu Chen Wang Wen Shen Yunyang Wang Bin Wang |
| author_facet | Shan Wang Shasha Jiang Xu Li Huan Huang Xu Qiu Meng Yu Xiaoli Yang Fengjun Liu Chen Wang Wen Shen Yunyang Wang Bin Wang |
| author_sort | Shan Wang |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer. |
| format | Article |
| id | doaj-art-ecb07c14cd5148de85786b9b2d42537c |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-ecb07c14cd5148de85786b9b2d42537c2025-08-20T02:38:26ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2423983FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironmentShan Wang0Shasha Jiang1Xu Li2Huan Huang3Xu Qiu4Meng Yu5Xiaoli Yang6Fengjun Liu7Chen Wang8Wen Shen9Yunyang Wang10Bin Wang11Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaQingdao Municipal Hospital, Qingdao, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao, ChinaGlioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2423983GBMpeptidesimmunotherapyMDSCsTregmicroglia |
| spellingShingle | Shan Wang Shasha Jiang Xu Li Huan Huang Xu Qiu Meng Yu Xiaoli Yang Fengjun Liu Chen Wang Wen Shen Yunyang Wang Bin Wang FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment OncoImmunology GBM peptides immunotherapy MDSCs Treg microglia |
| title | FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment |
| title_full | FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment |
| title_fullStr | FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment |
| title_full_unstemmed | FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment |
| title_short | FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment |
| title_sort | fgl2172 220 peptides improve the antitumor effect of hcmv ie1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment |
| topic | GBM peptides immunotherapy MDSCs Treg microglia |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2423983 |
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