Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodes
Background Immune checkpoint blockade is a promising anticancer therapy, whereas the presence of T cells in tumor sites is indispensable for its therapeutic efficacy. To promote the infiltration of T cells and dendritic cells (DCs) into the tumor, we previously proposed a local cell therapy using ch...
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BMJ Publishing Group
2024-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/12/e009683.full |
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| author | Yuichi Iida Mamoru Harada |
| author_facet | Yuichi Iida Mamoru Harada |
| author_sort | Yuichi Iida |
| collection | DOAJ |
| description | Background Immune checkpoint blockade is a promising anticancer therapy, whereas the presence of T cells in tumor sites is indispensable for its therapeutic efficacy. To promote the infiltration of T cells and dendritic cells (DCs) into the tumor, we previously proposed a local cell therapy using chemokine (C-C motif) ligand 19 (CCL19)-expressing immortalized syngeneic immortalized mesenchymal stem cells (syn-iMSC/CCL19). However, the preparation of syngeneic/autologous MSC from individual hosts limits the clinical application of this cell therapy.Methods In this study, we further developed a new cell therapy using allogeneic iMSC/CCL19 (allo-iMSC/CCL19) using several tumor mice models.Results The allo-iMSC/CCL19 therapy exerted drastic antitumor effects, in which the host’s T cells were induced to respond to allogeneic MSC. In addition, the allo-iMSC/CCL19 therapy promoted the infiltration of CD103+ interleukin (IL)-12-producing DCs and priming of CD8+ T cells at tumor sites compared with that using syn-iMSC/CCL19. The antitumor effect of allo-iMSC/CCL19 therapy was not influenced by fingolimod, a sphingosine 1-phosphate receptor modulator, implying no involvement of draining lymph nodes in the priming of tumor-specific T cells.Conclusion These results suggest that allo-iMSC/CCL19 therapy exerts dramatic antitumor effects by promoting the infiltration of CD103+ IL-12-producing DCs and thereby priming tumor-specific CD8+ T cells at tumor sites. This local cell therapy could be a promising approach to anticancer therapy, particularly for overcoming dysfunction in the cancer-immunity cycle. |
| format | Article |
| id | doaj-art-480a7459bf5e46d6b124191a4f91d327 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-480a7459bf5e46d6b124191a4f91d3272025-08-20T01:58:23ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-12-01121210.1136/jitc-2024-009683Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodesYuichi Iida0Mamoru Harada1Immunology, Shimane University Faculty of Medicine Graduate School of Medicine, Izumo, JapanImmunology, Shimane University Faculty of Medicine Graduate School of Medicine, Izumo, JapanBackground Immune checkpoint blockade is a promising anticancer therapy, whereas the presence of T cells in tumor sites is indispensable for its therapeutic efficacy. To promote the infiltration of T cells and dendritic cells (DCs) into the tumor, we previously proposed a local cell therapy using chemokine (C-C motif) ligand 19 (CCL19)-expressing immortalized syngeneic immortalized mesenchymal stem cells (syn-iMSC/CCL19). However, the preparation of syngeneic/autologous MSC from individual hosts limits the clinical application of this cell therapy.Methods In this study, we further developed a new cell therapy using allogeneic iMSC/CCL19 (allo-iMSC/CCL19) using several tumor mice models.Results The allo-iMSC/CCL19 therapy exerted drastic antitumor effects, in which the host’s T cells were induced to respond to allogeneic MSC. In addition, the allo-iMSC/CCL19 therapy promoted the infiltration of CD103+ interleukin (IL)-12-producing DCs and priming of CD8+ T cells at tumor sites compared with that using syn-iMSC/CCL19. The antitumor effect of allo-iMSC/CCL19 therapy was not influenced by fingolimod, a sphingosine 1-phosphate receptor modulator, implying no involvement of draining lymph nodes in the priming of tumor-specific T cells.Conclusion These results suggest that allo-iMSC/CCL19 therapy exerts dramatic antitumor effects by promoting the infiltration of CD103+ IL-12-producing DCs and thereby priming tumor-specific CD8+ T cells at tumor sites. This local cell therapy could be a promising approach to anticancer therapy, particularly for overcoming dysfunction in the cancer-immunity cycle.https://jitc.bmj.com/content/12/12/e009683.full |
| spellingShingle | Yuichi Iida Mamoru Harada Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodes Journal for ImmunoTherapy of Cancer |
| title | Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodes |
| title_full | Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodes |
| title_fullStr | Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodes |
| title_full_unstemmed | Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodes |
| title_short | Local cell therapy using CCL19-expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating CD103+ IL-12-producing dendritic cells and priming CD8+ T cells without involving draining lymph nodes |
| title_sort | local cell therapy using ccl19 expressing allogeneic mesenchymal stem cells exerts robust antitumor effects by accumulating cd103 il 12 producing dendritic cells and priming cd8 t cells without involving draining lymph nodes |
| url | https://jitc.bmj.com/content/12/12/e009683.full |
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