Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy
BackgroundA head and neck cancer organoid (HNCO) and peripheral blood T cell co-culture model was established to investigate whether HNCOs can induce the differentiation of peripheral blood T cells into tumor-reactive T cells. Additionally, this study seeks to explore the cytotoxicity of these T cel...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1573965/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332061558538240 |
|---|---|
| author | Yinyu Chen Yinyu Chen Shoupeng Wang Luxi Zheng Luxi Zheng Lin Chen Feng Xu Shuqi Guo Shuqi Guo Jian Meng Jian Meng Jian Meng |
| author_facet | Yinyu Chen Yinyu Chen Shoupeng Wang Luxi Zheng Luxi Zheng Lin Chen Feng Xu Shuqi Guo Shuqi Guo Jian Meng Jian Meng Jian Meng |
| author_sort | Yinyu Chen |
| collection | DOAJ |
| description | BackgroundA head and neck cancer organoid (HNCO) and peripheral blood T cell co-culture model was established to investigate whether HNCOs can induce the differentiation of peripheral blood T cells into tumor-reactive T cells. Additionally, this study seeks to explore the cytotoxicity of these T cells against autologous tumor organoids, providing theoretical and experimental evidence for the feasibility of this model as a platform for adoptive cell immunotherapy in head and neck cancer (HNC).MethodsHNCO single cells were co-cultured with peripheral blood lymphocytes (PBLs) collected and isolated from patients with HNC. The culture supernatant was collected and assayed for interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF- α). The expression of T cell activation markers cluster of differentiation (CD)137 and CD107a was measured by flow cytometry to confirm tumor specificity and cytotoxicity. Additionally, the optimal effector-to-target (E/T) ratio was determined using the Cell Counting Kit-8 assay, and HNCO killing was quantified by fluorescent labeling.ResultsOf the 27 successfully established HNCO-T cell co-culture systems, 81.48% induced the in vitro differentiation and tumor-reactive CD8+ T cell expansion capable of mediating the killing of mature HNCOs.ConclusionThe patient-derived HNCO-T cell co-culture model effectively induced PBL differentiation into tumor-reactive CD8+ T cells with enhanced tumor-killing activities. This model serves as a novel in vitro preclinical tool for advancing personalized adoptive immunotherapy in HNC. |
| format | Article |
| id | doaj-art-b8680e00eda4468988856db74a16bc6e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b8680e00eda4468988856db74a16bc6e2025-08-20T03:46:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15739651573965Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapyYinyu Chen0Yinyu Chen1Shoupeng Wang2Luxi Zheng3Luxi Zheng4Lin Chen5Feng Xu6Shuqi Guo7Shuqi Guo8Jian Meng9Jian Meng10Jian Meng11Department of Stomatology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaSchool of Stomatology, Xuzhou Medical University, Xuzhou, ChinaDepartment of Stomatology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaDepartment of Stomatology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaThe Xuzhou Clinical College of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, ChinaDepartment of Stomatology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaDepartment of Stomatology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaDepartment of Stomatology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaThe Xuzhou Clinical College of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, ChinaDepartment of Stomatology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaSchool of Stomatology, Xuzhou Medical University, Xuzhou, ChinaThe Xuzhou Clinical College of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, ChinaBackgroundA head and neck cancer organoid (HNCO) and peripheral blood T cell co-culture model was established to investigate whether HNCOs can induce the differentiation of peripheral blood T cells into tumor-reactive T cells. Additionally, this study seeks to explore the cytotoxicity of these T cells against autologous tumor organoids, providing theoretical and experimental evidence for the feasibility of this model as a platform for adoptive cell immunotherapy in head and neck cancer (HNC).MethodsHNCO single cells were co-cultured with peripheral blood lymphocytes (PBLs) collected and isolated from patients with HNC. The culture supernatant was collected and assayed for interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF- α). The expression of T cell activation markers cluster of differentiation (CD)137 and CD107a was measured by flow cytometry to confirm tumor specificity and cytotoxicity. Additionally, the optimal effector-to-target (E/T) ratio was determined using the Cell Counting Kit-8 assay, and HNCO killing was quantified by fluorescent labeling.ResultsOf the 27 successfully established HNCO-T cell co-culture systems, 81.48% induced the in vitro differentiation and tumor-reactive CD8+ T cell expansion capable of mediating the killing of mature HNCOs.ConclusionThe patient-derived HNCO-T cell co-culture model effectively induced PBL differentiation into tumor-reactive CD8+ T cells with enhanced tumor-killing activities. This model serves as a novel in vitro preclinical tool for advancing personalized adoptive immunotherapy in HNC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1573965/fulladoptive cell therapyperipheral blood T cellshead and neck cancerorganoidco-culture |
| spellingShingle | Yinyu Chen Yinyu Chen Shoupeng Wang Luxi Zheng Luxi Zheng Lin Chen Feng Xu Shuqi Guo Shuqi Guo Jian Meng Jian Meng Jian Meng Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy Frontiers in Immunology adoptive cell therapy peripheral blood T cells head and neck cancer organoid co-culture |
| title | Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy |
| title_full | Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy |
| title_fullStr | Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy |
| title_full_unstemmed | Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy |
| title_short | Generating tumor-specific T cells based on a head and neck cancer organoid for adoptive cell therapy |
| title_sort | generating tumor specific t cells based on a head and neck cancer organoid for adoptive cell therapy |
| topic | adoptive cell therapy peripheral blood T cells head and neck cancer organoid co-culture |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1573965/full |
| work_keys_str_mv | AT yinyuchen generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT yinyuchen generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT shoupengwang generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT luxizheng generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT luxizheng generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT linchen generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT fengxu generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT shuqiguo generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT shuqiguo generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT jianmeng generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT jianmeng generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy AT jianmeng generatingtumorspecifictcellsbasedonaheadandneckcancerorganoidforadoptivecelltherapy |