2024年1月24日，中国广州中山大学肿瘤医院南方肿瘤学国家重点实验室，广东省癌症临床研究中心Liang Kang ，Huashan Liu等老师在Nature Communications（IF=16.6）上，在线发表题为“Mutant KRAS-activated circATXN7 fosters tumor immunoescape by sensitizing tumor-specific T cells to activation-induced cell death”的论文，此论文使用了联科生物Annexin V-FITC试剂(货号;AP101-100-AVF），7-AAD试剂(货号;AP104-100-AAD）。

C Apoptosis of CTLs induced by anti-CD3 or autologous tumor cells (n = 4 samples; ****p ≤ 0.0001 compared with untreated day-6 CTLs by one-way ANOVA). D Apoptosis of CTLs induced by anti-CD3 or CEA-loaded T2 cells (T2/CEA) (n = 4 samples; ****p ≤ 0.0001 compared with untreated day-6 CTLs by one-way ANOVA). E Apoptosis of the CRC antigen-activated CTLs induced by autologous tumor cells preincubated with anti-HLA-I or IgG (n = 4 samples; ****p ≤ 0.0001 compared with IgG by one-way ANOVA). F Apoptosis of the CEA-specific CTLs induced by CEA-loaded T2 cells (T2/CEA) preincubated with anti-HLA-I or IgG (n = 4 samples; ****p ≤ 0.0001 compared with IgG by one-way ANOVA)

KRAS突变型（KRASMUT)癌症患者通常伴随着肿瘤免疫逃逸，然而潜在机制尚未研究清楚。我们报告了来自KRASMUT癌症的肿瘤特异性细胞毒性T淋巴细胞（CTLs）对激活诱导的细胞死亡（AICD）敏感。circATXN7是一种与核因子-κB（NF-κB）相互作用的环状RNA，通过失活NF-κB来控制T细胞对AICD的敏感性。从机制上讲，源自KRASMUT肿瘤细胞产生的乳酸导致组蛋白乳酸化，直接激活circATXN7的转录，circATXN7结合NF-κBP65蛋白亚单位并掩盖P65蛋白核定位信号基序，从而将其隔离在细胞质中。临床上，在肿瘤特异性CTLs中circATXN7的上调与不良临床结果和免疫治疗耐药相关。在CD8+ T细胞中遗传消除circATXN7导致突变选择性肿瘤抑制，同时还增加了雌性小鼠多种肿瘤模型中抗PD1的有效性。此外，靶向转移的肿瘤反应性CTLs中的circATXN7可以改善其抗肿瘤活性。这些发现为淋巴细胞表达的circRNA如何促进T细胞命运决定和抗癌免疫疗法提供了新的见解。

 

  

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参考文献：

Zhou, C., Li, W., Liang, Z. et al. Mutant KRAS-activated circATXN7 fosters tumor immunoescape by sensitizing tumor-specific T cells to activation-induced cell death. Nat Commun 15, 499 (2024).

原文链接：

https://www.nature.com/articles/s41467-024-44779-1#citeas