Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy
Abstract The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-024-02401-y |
| _version_ | 1797219592720875520 |
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| author | Wenqi Shen Yecheng Li Ziyi Yang Wenjing Li Yi Cao Yilin Liu Zheng Wang Renjun Pei Chungen Xing |
| author_facet | Wenqi Shen Yecheng Li Ziyi Yang Wenjing Li Yi Cao Yilin Liu Zheng Wang Renjun Pei Chungen Xing |
| author_sort | Wenqi Shen |
| collection | DOAJ |
| description | Abstract The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy. |
| first_indexed | 2024-04-24T12:36:06Z |
| format | Article |
| id | doaj.art-5a0d21155759485da32f64152e59d19b |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-24T12:36:06Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-5a0d21155759485da32f64152e59d19b2024-04-07T11:29:20ZengBMCJournal of Nanobiotechnology1477-31552024-04-0122111410.1186/s12951-024-02401-yTumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapyWenqi Shen0Yecheng Li1Ziyi Yang2Wenjing Li3Yi Cao4Yilin Liu5Zheng Wang6Renjun Pei7Chungen Xing8Department of General Surgery, Second Affiliated Hospital of Soochow UniversityDepartment of General Surgery, Second Affiliated Hospital of Soochow UniversityCAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of SciencesCAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of SciencesCAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of SciencesSchool of Intelligent Finance and Business, Entrepreneur College, Xi’an Jiaotong-Liverpool UniversityCAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of SciencesCAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of SciencesDepartment of General Surgery, Second Affiliated Hospital of Soochow UniversityAbstract The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.https://doi.org/10.1186/s12951-024-02401-yCancer-associated fibroblastsTumor microenvironmentIntratumoral penetrationColon cancerTumor immunotherapy |
| spellingShingle | Wenqi Shen Yecheng Li Ziyi Yang Wenjing Li Yi Cao Yilin Liu Zheng Wang Renjun Pei Chungen Xing Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy Journal of Nanobiotechnology Cancer-associated fibroblasts Tumor microenvironment Intratumoral penetration Colon cancer Tumor immunotherapy |
| title | Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy |
| title_full | Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy |
| title_fullStr | Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy |
| title_full_unstemmed | Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy |
| title_short | Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy |
| title_sort | tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy |
| topic | Cancer-associated fibroblasts Tumor microenvironment Intratumoral penetration Colon cancer Tumor immunotherapy |
| url | https://doi.org/10.1186/s12951-024-02401-y |
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