Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy
For clinical application by dendritic cell (DC)-based cancer immunotherapy, a proper adjuvant system to elicit a strong anticancer immune response is needed. Here, we investigated the potential of chorismate mutase (TBCM, Rv1885c), a putative Mycobacterium tuberculosis (TB) virulence factor, as an i...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2021.2023340 |
| _version_ | 1818332472862048256 |
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| author | Hyein Jeong So-Young Lee Hyejun Seo Dong Hyun Kim Duhyung Lee Bum-Joon Kim |
| author_facet | Hyein Jeong So-Young Lee Hyejun Seo Dong Hyun Kim Duhyung Lee Bum-Joon Kim |
| author_sort | Hyein Jeong |
| collection | DOAJ |
| description | For clinical application by dendritic cell (DC)-based cancer immunotherapy, a proper adjuvant system to elicit a strong anticancer immune response is needed. Here, we investigated the potential of chorismate mutase (TBCM, Rv1885c), a putative Mycobacterium tuberculosis (TB) virulence factor, as an immunoadjuvant in DC-based tumor immunotherapy. First, we found that TBCM functionally activated DCs by upregulating costimulatory molecules, increasing the secretion of proinflammatory cytokines, enhancing migration and inducing the Th1-type immune response in a dose-dependent manner via TLR4-mediated signaling. In addition, subcutaneous injection of TBCM-activated DCs loaded with cell lysates led to reduced tumor mass, enhanced mouse survival and lowered tumor incidence in lung carcinoma (LLC) cell-bearing mice. This is mainly mediated by functional cytotoxic T lymphocyte-mediated oncolytic activity and inhibition of cancer proliferation- and metastasis-related genes. Moreover, TBCM-induced DCs can also generate memory CD4 T cells and exert long-term tumor prevention effects. In conclusion, our findings suggest that TBCM (Rv1885c), a novel TLR4 agonist, could be used as an immunoadjuvant for DC-based cancer immunotherapy. |
| first_indexed | 2024-12-13T13:36:18Z |
| format | Article |
| id | doaj.art-ebe604b364d042319f8b876beb2eab6a |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T13:36:18Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-ebe604b364d042319f8b876beb2eab6a2022-12-21T23:43:48ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2021.20233402023340Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapyHyein Jeong0So-Young Lee1Hyejun Seo2Dong Hyun Kim3Duhyung Lee4Bum-Joon Kim5Seoul National UniversitySeoul National UniversitySeoul National UniversitySeoul National UniversitySeoul National UniversitySeoul National UniversityFor clinical application by dendritic cell (DC)-based cancer immunotherapy, a proper adjuvant system to elicit a strong anticancer immune response is needed. Here, we investigated the potential of chorismate mutase (TBCM, Rv1885c), a putative Mycobacterium tuberculosis (TB) virulence factor, as an immunoadjuvant in DC-based tumor immunotherapy. First, we found that TBCM functionally activated DCs by upregulating costimulatory molecules, increasing the secretion of proinflammatory cytokines, enhancing migration and inducing the Th1-type immune response in a dose-dependent manner via TLR4-mediated signaling. In addition, subcutaneous injection of TBCM-activated DCs loaded with cell lysates led to reduced tumor mass, enhanced mouse survival and lowered tumor incidence in lung carcinoma (LLC) cell-bearing mice. This is mainly mediated by functional cytotoxic T lymphocyte-mediated oncolytic activity and inhibition of cancer proliferation- and metastasis-related genes. Moreover, TBCM-induced DCs can also generate memory CD4 T cells and exert long-term tumor prevention effects. In conclusion, our findings suggest that TBCM (Rv1885c), a novel TLR4 agonist, could be used as an immunoadjuvant for DC-based cancer immunotherapy.http://dx.doi.org/10.1080/2162402X.2021.2023340mycobacterium tuberculosischorismate mutase (tbcm)tlr4 agonistdendritic cellscancer immunotherapyadjuvant |
| spellingShingle | Hyein Jeong So-Young Lee Hyejun Seo Dong Hyun Kim Duhyung Lee Bum-Joon Kim Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy OncoImmunology mycobacterium tuberculosis chorismate mutase (tbcm) tlr4 agonist dendritic cells cancer immunotherapy adjuvant |
| title | Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy |
| title_full | Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy |
| title_fullStr | Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy |
| title_full_unstemmed | Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy |
| title_short | Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy |
| title_sort | potential of mycobacterium tuberculosis chorismate mutase rv1885c as a novel tlr4 mediated adjuvant for dendritic cell based cancer immunotherapy |
| topic | mycobacterium tuberculosis chorismate mutase (tbcm) tlr4 agonist dendritic cells cancer immunotherapy adjuvant |
| url | http://dx.doi.org/10.1080/2162402X.2021.2023340 |
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