Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy
BackgroundImmunotherapy, especially with the use of immune checkpoint inhibitors, has demonstrated efficacy for a variety of malignant tumors. However, the potential of immunotherapy for endometrial cancer (EC) with POLE mutations remains underexplored.MethodsWe utilized multiple databases and clini...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528532/full |
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| author | Jian Huang Shuangna Song Yihua Yin Yinyan He Huimin Wang Ye Gu Laman He Xintao Wang Xiaocao Miao Zhigang Zhang Xueli Zhang Yiran Li Yiran Li |
| author_facet | Jian Huang Shuangna Song Yihua Yin Yinyan He Huimin Wang Ye Gu Laman He Xintao Wang Xiaocao Miao Zhigang Zhang Xueli Zhang Yiran Li Yiran Li |
| author_sort | Jian Huang |
| collection | DOAJ |
| description | BackgroundImmunotherapy, especially with the use of immune checkpoint inhibitors, has demonstrated efficacy for a variety of malignant tumors. However, the potential of immunotherapy for endometrial cancer (EC) with POLE mutations remains underexplored.MethodsWe utilized multiple databases and clinical specimens to investigate the immunogenicity profiles of EC patients carrying POLE mutations. One particular hotspot mutation POLEP286R was identified and further studied. Consequently, by constructing human leukocyte antigen (HLA) tetramers and incubating them with patients’ peripheral blood mononuclear cells (PBMCs), T cells capable of recognizing the POLEP286R mutation were sorted for further transcriptomic, proteomic and T-cell receptor (TCR) sequencing analyses and for an organoid EC model.ResultsTumor- and immune-related pathways were shown to be activated in the POLEP286R mutant group. Importantly, by using an organoid model of EC, we further confirmed the antitumor potential of T cells that were specific to the POLEP286R mutation.ConclusionsOur study uncovers the pronounced immunogenicity of POLE-mutant EC and characterizes neoantigens that are unique to the POLEP286R mutation, thus providing a promising new immunotherapeutic strategy for EC. |
| format | Article |
| id | doaj-art-6d561111a2214b2c988c3597bab2f782 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-6d561111a2214b2c988c3597bab2f7822025-01-27T06:40:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15285321528532Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapyJian Huang0Shuangna Song1Yihua Yin2Yinyan He3Huimin Wang4Ye Gu5Laman He6Xintao Wang7Xiaocao Miao8Zhigang Zhang9Xueli Zhang10Yiran Li11Yiran Li12Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, ChinaCenter for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, ChinaBackgroundImmunotherapy, especially with the use of immune checkpoint inhibitors, has demonstrated efficacy for a variety of malignant tumors. However, the potential of immunotherapy for endometrial cancer (EC) with POLE mutations remains underexplored.MethodsWe utilized multiple databases and clinical specimens to investigate the immunogenicity profiles of EC patients carrying POLE mutations. One particular hotspot mutation POLEP286R was identified and further studied. Consequently, by constructing human leukocyte antigen (HLA) tetramers and incubating them with patients’ peripheral blood mononuclear cells (PBMCs), T cells capable of recognizing the POLEP286R mutation were sorted for further transcriptomic, proteomic and T-cell receptor (TCR) sequencing analyses and for an organoid EC model.ResultsTumor- and immune-related pathways were shown to be activated in the POLEP286R mutant group. Importantly, by using an organoid model of EC, we further confirmed the antitumor potential of T cells that were specific to the POLEP286R mutation.ConclusionsOur study uncovers the pronounced immunogenicity of POLE-mutant EC and characterizes neoantigens that are unique to the POLEP286R mutation, thus providing a promising new immunotherapeutic strategy for EC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528532/fullendometrial cancer (EC)POLEtumor neoantigensimmunotherapyCD8+ T cells |
| spellingShingle | Jian Huang Shuangna Song Yihua Yin Yinyan He Huimin Wang Ye Gu Laman He Xintao Wang Xiaocao Miao Zhigang Zhang Xueli Zhang Yiran Li Yiran Li Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy Frontiers in Immunology endometrial cancer (EC) POLE tumor neoantigens immunotherapy CD8+ T cells |
| title | Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy |
| title_full | Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy |
| title_fullStr | Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy |
| title_full_unstemmed | Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy |
| title_short | Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy |
| title_sort | unveiling immunogenic characteristics and neoantigens in endometrial cancer with pole hotspot mutations for improved immunotherapy |
| topic | endometrial cancer (EC) POLE tumor neoantigens immunotherapy CD8+ T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528532/full |
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