Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells
Abstract Background Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial malignancy. It is characterized by insufficient infiltration of anti-tumor T lymphocytes within the tumor microenvironment (TME), rendering it an “immune cold” disease. This immune deficiency res...
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06194-y |
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| author | Guochen Li Haiyan Yang Tengfei Ke Na Tan Xiaolan Du Xirui Duan Xinyan Zhou Guangrong Zheng Chengde Liao |
| author_facet | Guochen Li Haiyan Yang Tengfei Ke Na Tan Xiaolan Du Xirui Duan Xinyan Zhou Guangrong Zheng Chengde Liao |
| author_sort | Guochen Li |
| collection | DOAJ |
| description | Abstract Background Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial malignancy. It is characterized by insufficient infiltration of anti-tumor T lymphocytes within the tumor microenvironment (TME), rendering it an “immune cold” disease. This immune deficiency results in poor responses to immune checkpoint blockade (ICB) therapies. Recent studies have demonstrated that bacteria can proliferate within tumors and activate immune responses. Therefore, in this study, we employed Escherichia coli (E. coli) in combination with anti-PD-1 antibodies to treat GBM, with the aim of exploring the immune-activating potential of E. coli in GBM and its synergistic effect on anti-PD-1 therapy. Methods The E. coli and anti-PD-1 antibody therapy were administered intravenously and intraperitoneally, respectively. Complete blood cell count, blood biochemical analysis, hematoxylin and eosin (H&E) staining, and agar plate culture were employed to evaluate the biosafety and tumor-targeting capability of E. coli. ELISA kits were used to detect innate immune cytokines. Flow cytometry and immunofluorescence staining were used to investigate T cells. Tumor volume of tumor-bearing mice was recorded to evaluate the combined treatment efficacy. H&E staining and immunofluorescence staining were used to observe the tumor inhibition markers. Results E.coli can specifically target into the tumor region, and activate the innate immune response in mice. Immunofluorescence staining and flow cytometry results demonstrated that the combination treatment group exhibited a significant upregulation of cytotoxic CD8+ T cells and a marked suppression of regulatory T cells compared to the control group. The expression of Ki67 was significantly downregulated, and TUNEL staining revealed an increased number of apoptotic cells in the combination treatment group. Furthermore, the tumor growth rate in the combination treatment group was significantly slower than that in the control group. Conclusions E. coli exhibits potential anti-tumor activity and can activate the innate immune response and further regulate immune cells in the tumor tissues to synergize the effect of anti-PD-1 therapy on GBM, providing new insights to enhance the efficacy of GBM immunotherapy. |
| format | Article |
| id | doaj-art-b94b8ac429264eb9a5e3328167ffbddb |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-b94b8ac429264eb9a5e3328167ffbddb2025-02-09T12:52:24ZengBMCJournal of Translational Medicine1479-58762025-02-0123111310.1186/s12967-025-06194-yEscherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cellsGuochen Li0Haiyan Yang1Tengfei Ke2Na Tan3Xiaolan Du4Xirui Duan5Xinyan Zhou6Guangrong Zheng7Chengde Liao8Department of Radiology, Yan’an Hospital of Kunming City (Yan’an Hospital Affiliated to Kunming Medical University, Yunnan Cardiovascular Hospital)Department of Ultrasound, Chongqing General Hospital, Chongqing UniversityDepartment of Radiology, Yunnan Cancer Hospital (The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan Campus)Department of Radiology, Yan’an Hospital of Kunming City (Yan’an Hospital Affiliated to Kunming Medical University, Yunnan Cardiovascular Hospital)Department of Radiology, Yan’an Hospital of Kunming City (Yan’an Hospital Affiliated to Kunming Medical University, Yunnan Cardiovascular Hospital)Department of Radiology, Yan’an Hospital of Kunming City (Yan’an Hospital Affiliated to Kunming Medical University, Yunnan Cardiovascular Hospital)Department of Radiology, Yan’an Hospital of Kunming City (Yan’an Hospital Affiliated to Kunming Medical University, Yunnan Cardiovascular Hospital)Department of Radiology, Yan’an Hospital of Kunming City (Yan’an Hospital Affiliated to Kunming Medical University, Yunnan Cardiovascular Hospital)Department of Radiology, Yan’an Hospital of Kunming City (Yan’an Hospital Affiliated to Kunming Medical University, Yunnan Cardiovascular Hospital)Abstract Background Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial malignancy. It is characterized by insufficient infiltration of anti-tumor T lymphocytes within the tumor microenvironment (TME), rendering it an “immune cold” disease. This immune deficiency results in poor responses to immune checkpoint blockade (ICB) therapies. Recent studies have demonstrated that bacteria can proliferate within tumors and activate immune responses. Therefore, in this study, we employed Escherichia coli (E. coli) in combination with anti-PD-1 antibodies to treat GBM, with the aim of exploring the immune-activating potential of E. coli in GBM and its synergistic effect on anti-PD-1 therapy. Methods The E. coli and anti-PD-1 antibody therapy were administered intravenously and intraperitoneally, respectively. Complete blood cell count, blood biochemical analysis, hematoxylin and eosin (H&E) staining, and agar plate culture were employed to evaluate the biosafety and tumor-targeting capability of E. coli. ELISA kits were used to detect innate immune cytokines. Flow cytometry and immunofluorescence staining were used to investigate T cells. Tumor volume of tumor-bearing mice was recorded to evaluate the combined treatment efficacy. H&E staining and immunofluorescence staining were used to observe the tumor inhibition markers. Results E.coli can specifically target into the tumor region, and activate the innate immune response in mice. Immunofluorescence staining and flow cytometry results demonstrated that the combination treatment group exhibited a significant upregulation of cytotoxic CD8+ T cells and a marked suppression of regulatory T cells compared to the control group. The expression of Ki67 was significantly downregulated, and TUNEL staining revealed an increased number of apoptotic cells in the combination treatment group. Furthermore, the tumor growth rate in the combination treatment group was significantly slower than that in the control group. Conclusions E. coli exhibits potential anti-tumor activity and can activate the innate immune response and further regulate immune cells in the tumor tissues to synergize the effect of anti-PD-1 therapy on GBM, providing new insights to enhance the efficacy of GBM immunotherapy.https://doi.org/10.1186/s12967-025-06194-yGlioblastomaPD-1Escherichia coliImmunotherapySynergy |
| spellingShingle | Guochen Li Haiyan Yang Tengfei Ke Na Tan Xiaolan Du Xirui Duan Xinyan Zhou Guangrong Zheng Chengde Liao Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells Journal of Translational Medicine Glioblastoma PD-1 Escherichia coli Immunotherapy Synergy |
| title | Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells |
| title_full | Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells |
| title_fullStr | Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells |
| title_full_unstemmed | Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells |
| title_short | Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells |
| title_sort | escherichia coli combination with pd 1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells |
| topic | Glioblastoma PD-1 Escherichia coli Immunotherapy Synergy |
| url | https://doi.org/10.1186/s12967-025-06194-y |
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