Lisha Ma , Xiya Wang , Qianjing Zhang , Zhaoya Gao , Xiangwen Ji , Zhilang Li , Yixian Li , Pengchong Zhang , Xuan Che , Yun Sun , Yun Bai , Hongkui Deng
{"title":"利用自体结直肠肿瘤类器官改进循环淋巴细胞中肿瘤特异性tcr的鉴定","authors":"Lisha Ma , Xiya Wang , Qianjing Zhang , Zhaoya Gao , Xiangwen Ji , Zhilang Li , Yixian Li , Pengchong Zhang , Xuan Che , Yun Sun , Yun Bai , Hongkui Deng","doi":"10.1016/j.canlet.2025.218036","DOIUrl":null,"url":null,"abstract":"<div><div>The identification of effective T cell receptors (TCRs) with specific reactivity against tumor cells is critical for the efficacy of TCR-engineered T cell therapy. However, different approaches for screening effective TCRs remain to be explored. We developed an optimized approach to identify effective TCRs based on an organoid culture system with patient-derived tumor cells in the presence of oxaliplatin and autologous dendritic cells. By coculturing the immunogenic debris of patient tumor cells from the organoid, we successfully enriched tumor-reactive CD4<sup>+</sup> and CD8<sup>+</sup> T cells, enhanced the activation and proliferation of T cells, and could facilitate the identification of tumor-reactive CD8<sup>+</sup> T cells from patients with MHC I-downregulated tumors. We further used autologous tumor organoids to verify that candidate tumor-specific TCRs can elicit patient-specific tumor recognition and killing when expressed in allogeneic T cells. Our organoid-based tumor-reactive T cell enrichment system and TCR screening validation platform provide an empirical strategy for the isolation of tumor-reactive T cells and can advance the study of TCR-engineered T cell therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"633 ","pages":"Article 218036"},"PeriodicalIF":10.1000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Improved identification of tumor-specific TCRs from circulating lymphocytes using autologous colorectal tumor organoids\",\"authors\":\"Lisha Ma , Xiya Wang , Qianjing Zhang , Zhaoya Gao , Xiangwen Ji , Zhilang Li , Yixian Li , Pengchong Zhang , Xuan Che , Yun Sun , Yun Bai , Hongkui Deng\",\"doi\":\"10.1016/j.canlet.2025.218036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The identification of effective T cell receptors (TCRs) with specific reactivity against tumor cells is critical for the efficacy of TCR-engineered T cell therapy. However, different approaches for screening effective TCRs remain to be explored. We developed an optimized approach to identify effective TCRs based on an organoid culture system with patient-derived tumor cells in the presence of oxaliplatin and autologous dendritic cells. By coculturing the immunogenic debris of patient tumor cells from the organoid, we successfully enriched tumor-reactive CD4<sup>+</sup> and CD8<sup>+</sup> T cells, enhanced the activation and proliferation of T cells, and could facilitate the identification of tumor-reactive CD8<sup>+</sup> T cells from patients with MHC I-downregulated tumors. We further used autologous tumor organoids to verify that candidate tumor-specific TCRs can elicit patient-specific tumor recognition and killing when expressed in allogeneic T cells. Our organoid-based tumor-reactive T cell enrichment system and TCR screening validation platform provide an empirical strategy for the isolation of tumor-reactive T cells and can advance the study of TCR-engineered T cell therapy.</div></div>\",\"PeriodicalId\":9506,\"journal\":{\"name\":\"Cancer letters\",\"volume\":\"633 \",\"pages\":\"Article 218036\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2025-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0304383525006068\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0304383525006068","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Improved identification of tumor-specific TCRs from circulating lymphocytes using autologous colorectal tumor organoids
The identification of effective T cell receptors (TCRs) with specific reactivity against tumor cells is critical for the efficacy of TCR-engineered T cell therapy. However, different approaches for screening effective TCRs remain to be explored. We developed an optimized approach to identify effective TCRs based on an organoid culture system with patient-derived tumor cells in the presence of oxaliplatin and autologous dendritic cells. By coculturing the immunogenic debris of patient tumor cells from the organoid, we successfully enriched tumor-reactive CD4+ and CD8+ T cells, enhanced the activation and proliferation of T cells, and could facilitate the identification of tumor-reactive CD8+ T cells from patients with MHC I-downregulated tumors. We further used autologous tumor organoids to verify that candidate tumor-specific TCRs can elicit patient-specific tumor recognition and killing when expressed in allogeneic T cells. Our organoid-based tumor-reactive T cell enrichment system and TCR screening validation platform provide an empirical strategy for the isolation of tumor-reactive T cells and can advance the study of TCR-engineered T cell therapy.
期刊介绍:
Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research.
Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy.
By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.