Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine
Abstract The nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG, also known as THIO) is a telomere-targeting agent with important clinical potency. It can selectively kill telomerase-positive tumor cells. We previously reported that THIO could successfully induce immunogenic cell death (IC...
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BMC
2025-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03471-2 |
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| author | Jing Bai Mengzhen Wang Yiming Luo Biao Duan Ying Yang Yuting Fu Shuqin Li Zhongqian Yang Peng Zheng Tong Yu Xin Yin Hongmei Bai Qiong Long Yanbing Ma |
| author_facet | Jing Bai Mengzhen Wang Yiming Luo Biao Duan Ying Yang Yuting Fu Shuqin Li Zhongqian Yang Peng Zheng Tong Yu Xin Yin Hongmei Bai Qiong Long Yanbing Ma |
| author_sort | Jing Bai |
| collection | DOAJ |
| description | Abstract The nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG, also known as THIO) is a telomere-targeting agent with important clinical potency. It can selectively kill telomerase-positive tumor cells. We previously reported that THIO could successfully induce immunogenic cell death (ICD) in multiple mouse tumor cell lines. In this study, we further explored the potential impact of THIO on remodeling the tumor microenvironment, regulating anti-tumor immune responses, and its possible synergistic effects with other therapeutic methods, such as tumor vaccines. Our results showed that THIO could also induce ICD in various human tumor cell lines. The induction of ICD in tumor cells promoted the migration and maturation of antigen-presenting cells. Administration of THIO significantly inhibited the growth of established CT26 and TC-1 tumors in mice. Meanwhile, it enhanced the anti-tumor CTL response and reduced the levels of immunosuppressive myeloid-derived suppressor cells (MDSCs) in both the spleen and tumor tissues. Additionally, THIO had a direct inhibitory effect on the proliferation and differentiation of MDSCs. Moreover, when combined with bacterial biomimetic vesicles or a nanovaccine, such as THIO with BBV or different Q11-tumor antigen peptide nanofibers, it exhibited enhanced anti-tumor effects and immune responses compared to monotherapy in either “immune hot” TC-1 tumors or “immune cold” B16-F10 tumors. In summary, THIO has the ability to remodel the tumor microenvironment, exert a specific killing effect on tumor cells, and effectively cooperate with tumor vaccines. This broadens the anti-tumor mechanisms of THIO and provides a promising strategy for improving anti-tumor immunotherapies. Graphical abstract |
| format | Article |
| id | doaj-art-e2d1eaca086a42e8bb1c1b6bfa01244f |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-e2d1eaca086a42e8bb1c1b6bfa01244f2025-08-20T03:10:41ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123112110.1186/s12951-025-03471-2Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccineJing Bai0Mengzhen Wang1Yiming Luo2Biao Duan3Ying Yang4Yuting Fu5Shuqin Li6Zhongqian Yang7Peng Zheng8Tong Yu9Xin Yin10Hongmei Bai11Qiong Long12Yanbing Ma13Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeKunming Medical UniversityKunming Medical UniversityInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeKunming Medical UniversityInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract The nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG, also known as THIO) is a telomere-targeting agent with important clinical potency. It can selectively kill telomerase-positive tumor cells. We previously reported that THIO could successfully induce immunogenic cell death (ICD) in multiple mouse tumor cell lines. In this study, we further explored the potential impact of THIO on remodeling the tumor microenvironment, regulating anti-tumor immune responses, and its possible synergistic effects with other therapeutic methods, such as tumor vaccines. Our results showed that THIO could also induce ICD in various human tumor cell lines. The induction of ICD in tumor cells promoted the migration and maturation of antigen-presenting cells. Administration of THIO significantly inhibited the growth of established CT26 and TC-1 tumors in mice. Meanwhile, it enhanced the anti-tumor CTL response and reduced the levels of immunosuppressive myeloid-derived suppressor cells (MDSCs) in both the spleen and tumor tissues. Additionally, THIO had a direct inhibitory effect on the proliferation and differentiation of MDSCs. Moreover, when combined with bacterial biomimetic vesicles or a nanovaccine, such as THIO with BBV or different Q11-tumor antigen peptide nanofibers, it exhibited enhanced anti-tumor effects and immune responses compared to monotherapy in either “immune hot” TC-1 tumors or “immune cold” B16-F10 tumors. In summary, THIO has the ability to remodel the tumor microenvironment, exert a specific killing effect on tumor cells, and effectively cooperate with tumor vaccines. This broadens the anti-tumor mechanisms of THIO and provides a promising strategy for improving anti-tumor immunotherapies. Graphical abstracthttps://doi.org/10.1186/s12951-025-03471-26-thio-2′-deoxyguanosine (THIO)Immunogenic cell death (ICD)Tumor immunotherapyCancer vaccineTumor microenvironment |
| spellingShingle | Jing Bai Mengzhen Wang Yiming Luo Biao Duan Ying Yang Yuting Fu Shuqin Li Zhongqian Yang Peng Zheng Tong Yu Xin Yin Hongmei Bai Qiong Long Yanbing Ma Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine Journal of Nanobiotechnology 6-thio-2′-deoxyguanosine (THIO) Immunogenic cell death (ICD) Tumor immunotherapy Cancer vaccine Tumor microenvironment |
| title | Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine |
| title_full | Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine |
| title_fullStr | Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine |
| title_full_unstemmed | Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine |
| title_short | Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine |
| title_sort | tumor microenvironment remodeling with a telomere targeting agent and its cooperative antitumor effects with a nanovaccine |
| topic | 6-thio-2′-deoxyguanosine (THIO) Immunogenic cell death (ICD) Tumor immunotherapy Cancer vaccine Tumor microenvironment |
| url | https://doi.org/10.1186/s12951-025-03471-2 |
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