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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-Immune-On-Chip to Evaluate Pathophysiological Feature of T Lymphocytes Expanded from Patient Tumors and Lymph Node Tissues.
Tumor-Immune-On-Chip to Evaluate Pathophysiological Feature of T Lymphocytes Expanded from Patient Tumors and Lymph Node Tissues.
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T淋巴细胞的浸润和细胞毒性对癌症免疫治疗疗效至关重要;然而,这些免疫细胞的行为尚未得到充分研究。在此,利用从一名结直肠癌患者组织中获取的细胞建立了一个肿瘤-免疫-芯片,以监测T淋巴细胞。通过该肿瘤-免疫-芯片,研究了肿瘤球体与来自肿瘤扩增的T淋巴细胞(TIL(肿瘤浸润淋巴细胞);TILs)或来自淋巴结的淋巴细胞(淋巴结来源淋巴细胞;LN T细胞)之间的相互作用。尽管最初的24小时分析未显示统计学差异,但延长至48小时的观察揭示了TILs和LN T细胞在T细胞介导的细胞死亡信号方面存在显著差异。48小时后,TILs表现出比LN T细胞更强的细胞毒性作用。与LN T细胞共培养相比,TIL共培养中肿瘤浸润CD3+细胞数量和cleaved caspase-3表达水平分别高4倍和2.1倍。
因此,这一概念验证平台使我们能够探索患者特异性的肿瘤-免疫微环境,重点关注不同类型的T淋巴细胞,并为未来的临床应用建立方法学。ClinicalTrials.gov标识符:NCT02589496。
The infiltration and cytotoxicity of T lymphocytes are critical for cancer immunotherapy efficacy; however, the behavior of these immune cells has not been thoroughly investigated.
Herein, a Tumor-Immune-On-Chip is established using cells acquired from the tissues of a patient with colorectal cancer to monitor T lymphocytes. Through the Tumor-Immune-On-Chip, the interaction between tumor spheroid and either T lymphocytes expanded from tumors (tumor-infiltrating lymphocytes; TILs) or lymph nodes (lymph node-derived lymphocytes; LN T cells) are investigated.
Although initial 24-h analysis showed no statistical differences, extended 48-h observation revealed a significant deviation in T cell-mediated cell death signals between TILs and LN T cells. TILs demonstrated more potent cytotoxic effects than LN T cells after 48 h. The number of tumor-infiltrating CD3 + cells and cleaved caspase-3 expression levels were 4- and 2. 1-fold higher, respectively, in TIL co-cultures compared to LN T cell co-cultures.
Therefore, this proof-of-concept platform allows us to explore the patient-specific tumor-immune microenvironment, focusing on different types of T lymphocytes and establishing methodology for future clinical applications. ClinicalTrial. gov identifier: NCT02589496.
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