Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor
Gastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immuno...
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| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2406576 |
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| author | Bo He Larissa Dymond Kira H. Wood Edward R. Bastow Jiulia Satiaputra Ji Li Anna Johansson-Percival Juliana Hamzah M. Priyanthi Kumarasinghe Mohammed Ballal Jonathan Foo Mikael Johansson Hooi C. Ee Scott W. White Louise Winteringham Ruth Ganss |
| author_facet | Bo He Larissa Dymond Kira H. Wood Edward R. Bastow Jiulia Satiaputra Ji Li Anna Johansson-Percival Juliana Hamzah M. Priyanthi Kumarasinghe Mohammed Ballal Jonathan Foo Mikael Johansson Hooi C. Ee Scott W. White Louise Winteringham Ruth Ganss |
| author_sort | Bo He |
| collection | DOAJ |
| description | Gastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immunotherapy. Specifically, we assessed the ability of a cancer vascular targeting peptide (VTP) to bind to mouse and patient GIST angiogenic blood vessels and deliver the TNF superfamily member LIGHT (TNFS14) into tumors. LIGHT-VTP treatment of GIST in humanized mice improved vascular function and tumor oxygenation, which correlated with an overall increase in intratumoral human effector T cells. Concomitant with LIGHT-mediated vascular remodeling, we observed intratumoral high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), which resemble spontaneous TLS found in GIST patients. Thus, by overcoming the limitations of immunodeficient xenograft models, we demonstrate the therapeutic feasibility of vascular targeting and immune priming in human GIST. Since TLS positively correlate with patient prognosis and improved response to immune checkpoint inhibition, vascular LIGHT targeting in GIST is a highly translatable approach to improve immunotherapeutic outcomes. |
| format | Article |
| id | doaj-art-5f92efd8788044f3a874c385746f567f |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-5f92efd8788044f3a874c385746f567f2024-12-03T13:49:34ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2406576Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumorBo He0Larissa Dymond1Kira H. Wood2Edward R. Bastow3Jiulia Satiaputra4Ji Li5Anna Johansson-Percival6Juliana Hamzah7M. Priyanthi Kumarasinghe8Mohammed Ballal9Jonathan Foo10Mikael Johansson11Hooi C. Ee12Scott W. White13Louise Winteringham14Ruth Ganss15Cancer Microenvironment Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaTranslational Cancer Research Program, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaCancer Microenvironment Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaCancer Microenvironment Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaCancer Microenvironment Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaCancer Microenvironment Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaCancer Microenvironment Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaImaging & Therapy Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaDepartment of Anatomical Pathology, PathWest QEII Medical Centre, Perth, Western AustraliaDepartment of General Surgery, Fiona Stanley Hospital, Western Australia, AustraliaDivision of Surgery, School of Medicine, University of Western Australia, Western Australia, AustraliaSir Charles Gairdner Hospital, QEII Medical Centre, Perth, Western Australia, AustraliaSir Charles Gairdner Hospital, QEII Medical Centre, Perth, Western Australia, AustraliaDivision of Obstetrics and Gynaecology, Faculty of Medicine, Dentistry, and Health Sciences, The University of Western Australia, Perth, Western Australia, AustraliaTranslational Cancer Research Program, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaCancer Microenvironment Laboratory, Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, AustraliaGastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immunotherapy. Specifically, we assessed the ability of a cancer vascular targeting peptide (VTP) to bind to mouse and patient GIST angiogenic blood vessels and deliver the TNF superfamily member LIGHT (TNFS14) into tumors. LIGHT-VTP treatment of GIST in humanized mice improved vascular function and tumor oxygenation, which correlated with an overall increase in intratumoral human effector T cells. Concomitant with LIGHT-mediated vascular remodeling, we observed intratumoral high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), which resemble spontaneous TLS found in GIST patients. Thus, by overcoming the limitations of immunodeficient xenograft models, we demonstrate the therapeutic feasibility of vascular targeting and immune priming in human GIST. Since TLS positively correlate with patient prognosis and improved response to immune checkpoint inhibition, vascular LIGHT targeting in GIST is a highly translatable approach to improve immunotherapeutic outcomes.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2406576Gastrointestinal tumor (GIST)humanized miceLIGHT (TNFS14)tertiary lymphoid structures (TLS)vascular targeting |
| spellingShingle | Bo He Larissa Dymond Kira H. Wood Edward R. Bastow Jiulia Satiaputra Ji Li Anna Johansson-Percival Juliana Hamzah M. Priyanthi Kumarasinghe Mohammed Ballal Jonathan Foo Mikael Johansson Hooi C. Ee Scott W. White Louise Winteringham Ruth Ganss Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor OncoImmunology Gastrointestinal tumor (GIST) humanized mice LIGHT (TNFS14) tertiary lymphoid structures (TLS) vascular targeting |
| title | Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor |
| title_full | Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor |
| title_fullStr | Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor |
| title_full_unstemmed | Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor |
| title_short | Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor |
| title_sort | immune priming and induction of tertiary lymphoid structures in a cord blood humanized mouse model of gastrointestinal stromal tumor |
| topic | Gastrointestinal tumor (GIST) humanized mice LIGHT (TNFS14) tertiary lymphoid structures (TLS) vascular targeting |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2406576 |
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