Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade
Abstract For medically inoperable non‐small cell lung cancer, microwave ablation (MWA) represents a super minimally invasive alternative treatment. However, tumor recurrence remains a concern. Here, it is demonstrated that the combination of MWA with Flt3L significantly inhibits tumor recurrence by...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202413181 |
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| author | Meixiang Wang Jing Sang Fengkuo Xu Shulong Wang Peng Liu Ji Ma Zhengtao Chen Qi Xie Zhigang Wei Xin Ye |
| author_facet | Meixiang Wang Jing Sang Fengkuo Xu Shulong Wang Peng Liu Ji Ma Zhengtao Chen Qi Xie Zhigang Wei Xin Ye |
| author_sort | Meixiang Wang |
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| description | Abstract For medically inoperable non‐small cell lung cancer, microwave ablation (MWA) represents a super minimally invasive alternative treatment. However, tumor recurrence remains a concern. Here, it is demonstrated that the combination of MWA with Flt3L significantly inhibits tumor recurrence by CD8+ central memory T (TCM)‐like cell‐dependent antitumor immune responses within the tumor‐draining lymph nodes (TdLN). TdLN‐TCM‐like cells encompassed both tumor‐specific memory T (TTSM) and progenitor‐exhausted T (TPEX) cells. The expansion of these cells markedly altered the differentiation of exhausted T cells within the tumor microenvironment (TME). TPEX predominantly differentiated into transitory effector‐like exhausted T cells (TEX‐int). The expansion of TTSM cells elicited by the combined therapy was reliant on conventional dendritic cells (cDCs) and was likely specifically dependent on the migratory cDC1s (Mig cDC1s) within the TdLN. The upregulation of ICOSL on migratory cDC1s was pivotal in initiating TTSM‐like cell‐mediated antitumor responses. Slc38a2 may be a critical gene responsible for the upregulation of ICOSL in Mig cDC1s following combined treatment. Finally, the combined treatment significantly enhanced the antitumor efficacy of immunotherapy based on PD‐1 blockade. The research thereby afforded a novel strategic approach to forestall tumor recurrence after MWA therapy, while also providing the foundational proof‐of‐concept for impending clinical investigations. |
| format | Article |
| id | doaj-art-7565294e4a0d42419365d7bd361d58eb |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-7565294e4a0d42419365d7bd361d58eb2025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202413181Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 BlockadeMeixiang Wang0Jing Sang1Fengkuo Xu2Shulong Wang3Peng Liu4Ji Ma5Zhengtao Chen6Qi Xie7Zhigang Wei8Xin Ye9Department of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaShandong Academy of Preventive Medicine Shandong Center for Disease Control and Prevention 16992 Jingshi Road Jinan 250014 P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaSchool of Laboratory Animal & Shandong Laboratory Animal Center Shandong First Medical University & Shandong Academy of Medical Sciences 6699 Qingdao Road Jinan 250014 P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Provincial Lab for Clinical Immunology Translational Medicine in Universities Shandong Lung Cancer Institute 16766 Jingshi Road Jinan 250014 P. R. ChinaAbstract For medically inoperable non‐small cell lung cancer, microwave ablation (MWA) represents a super minimally invasive alternative treatment. However, tumor recurrence remains a concern. Here, it is demonstrated that the combination of MWA with Flt3L significantly inhibits tumor recurrence by CD8+ central memory T (TCM)‐like cell‐dependent antitumor immune responses within the tumor‐draining lymph nodes (TdLN). TdLN‐TCM‐like cells encompassed both tumor‐specific memory T (TTSM) and progenitor‐exhausted T (TPEX) cells. The expansion of these cells markedly altered the differentiation of exhausted T cells within the tumor microenvironment (TME). TPEX predominantly differentiated into transitory effector‐like exhausted T cells (TEX‐int). The expansion of TTSM cells elicited by the combined therapy was reliant on conventional dendritic cells (cDCs) and was likely specifically dependent on the migratory cDC1s (Mig cDC1s) within the TdLN. The upregulation of ICOSL on migratory cDC1s was pivotal in initiating TTSM‐like cell‐mediated antitumor responses. Slc38a2 may be a critical gene responsible for the upregulation of ICOSL in Mig cDC1s following combined treatment. Finally, the combined treatment significantly enhanced the antitumor efficacy of immunotherapy based on PD‐1 blockade. The research thereby afforded a novel strategic approach to forestall tumor recurrence after MWA therapy, while also providing the foundational proof‐of‐concept for impending clinical investigations.https://doi.org/10.1002/advs.202413181dendritic cellsICOS‐ICOSL axismicrowave ablationnon‐small cell lung cancertumor‐specific memory CD8+ T cells |
| spellingShingle | Meixiang Wang Jing Sang Fengkuo Xu Shulong Wang Peng Liu Ji Ma Zhengtao Chen Qi Xie Zhigang Wei Xin Ye Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade Advanced Science dendritic cells ICOS‐ICOSL axis microwave ablation non‐small cell lung cancer tumor‐specific memory CD8+ T cells |
| title | Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade |
| title_full | Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade |
| title_fullStr | Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade |
| title_full_unstemmed | Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade |
| title_short | Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8+ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade |
| title_sort | microwave ablation combined with flt3l provokes tumor specific memory cd8 t cells mediated antitumor immunity in response to pd 1 blockade |
| topic | dendritic cells ICOS‐ICOSL axis microwave ablation non‐small cell lung cancer tumor‐specific memory CD8+ T cells |
| url | https://doi.org/10.1002/advs.202413181 |
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