RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
肿瘤细胞治疗研究
英文原题:Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs).
Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs).
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结直肠癌(CRC)是全球第三大常见癌症。TIL(肿瘤浸润淋巴细胞)(TILs)已被确定为CRC的重要预后标志物。TILs的治疗应用已在黑色素瘤和宫颈癌中显示出令人鼓舞的结果。
然而,其在CRC治疗中的应用仍处于探索阶段。目前尚无合适的体外模型来评估TIL疗效,这阻碍了该领域的进一步发展。患者来源的类器官(PDO)模型能够密切保留原肿瘤组织的特征并反映患者间异质性,为研究CRC与TILs之间的相互作用提供了极佳的平台。
本研究描述了一种从新鲜切除的肿瘤组织中建立患者来源的CRC类器官模型,随后分离和扩增TILs的方法。该系统允许CRC类器官与TILs共培养,从而能够评估TIL介导的细胞毒性和免疫反应。通过分析TIL对类器官的杀伤效果,可以预测基于TIL的免疫治疗用于个性化CRC治疗的可能结果。
此外,对TILs的进一步工程化改造可能增强其抗肿瘤疗效,为开发更有效的细胞疗法提供了有前景的策略。该PDO-TIL共培养模型为CRC中TIL疗法的临床前评估和个性化治疗策略提供了强有力的工具。
Colorectal cancer (CRC) is the third most common cancer worldwide. Tumor-infiltrating lymphocytes (TILs) have been identified as an important prognostic marker in CRC. The therapeutic application of TILs has already shown promising results in melanoma and cervical cancer.
However, their use in CRC therapy remains in an exploratory phase. A suitable in vitro model to evaluate TIL efficacy is currently unavailable, hindering further advancements in this field. Patient-derived organoid (PDO) models, which closely retain the characteristics of the original tumor tissue and reflect inter-patient heterogeneity, provide an excellent platform for studying the interaction between CRC and TILs.
In this study, a method is described to establish a patient-derived CRC organoid model from freshly resected tumor tissue, followed by isolation and expansion of TILs. This system allows co-culture of CRC organoids and TILs, enabling the assessment of TIL-mediated cytotoxicity and immune responses. By analyzing TIL killing efficacy on organoids, the potential outcomes of TIL-based immunotherapy for personalized CRC treatment can be predicted.
Moreover, further engineering of TILs may enhance their anti-tumor efficacy, offering a promising strategy for developing more effective cellular therapies. This PDO-TIL co-culture model provides a powerful tool for preclinical evaluation of TIL therapies and personalized treatment strategies in CRC.
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