Nie Haihang, Fang Shilin, Zhou Rui, Jia Yifan, Zhou Jingkai, Ning Yumei, Yu Yali, Hong Yuntian, Xu Fei, Zhao Qiu, Nie Jiayan, Wang Fan
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Hubei Provincial Clinical Research Center for Intestinal and Colorectal Diseases, Wuhan, China.
Cancer Med. 2025 Mar;14(6):e70802. doi: 10.1002/cam4.70802.
Immunotherapy is a promising and effective approach that has achieved significant curative effects in colorectal cancer (CRC). Recently, retinoic acid-inducible gene I (RIG-I) has been shown to play a critical role in tumor immunity. However, the correlation between RIG-I and immunotherapy in CRC remains unclear.
RIG-I expression was measured in CRC and normal samples based on analysis of the public databases, a tissue microarray, and CRC cell lines. The correlation between RIG-I and immune microenvironment was explored using well-established biological algorithms and in vitro and in vivo experiments.
We discovered that RIG-I expression was downregulated in CRC compared with normal samples. The bioinformatic algorithms indicated that high RIG-I-expressing samples showed a positive correlation with IFN-α response and enrichment of antitumor immune cells, especially CD8+ T cells. Furthermore, knockdown of RIG-I expression efficiently reduced the cell death, STAT1 phosphorylation, and CXCL10/11 expression induced by IFN-α in CRC cells. Finally, an in vivo study showed that the infiltration of CD3+ CD8+ T cells was significantly decreased in the RIG-I knockout group. An animal model further confirmed that the inhibition of tumor growth induced by IFN-α plus anti-PD-1 therapy was dependent on RIG-I expression.
RIG-I is a promising biomarker for CRC immunotherapy, which provides a novel concept for combinatorial immunotherapy.
免疫疗法是一种很有前景且有效的方法，已在结直肠癌（CRC）中取得显著疗效。最近，视黄酸诱导基因I（RIG-I）已被证明在肿瘤免疫中起关键作用。然而，RIG-I与CRC免疫疗法之间的相关性仍不清楚。
基于公共数据库分析、组织芯片和CRC细胞系，检测CRC和正常样本中RIG-I的表达。使用成熟的生物学算法以及体外和体内实验，探索RIG-I与免疫微环境之间的相关性。
我们发现，与正常样本相比，CRC中RIG-I的表达下调。生物信息学算法表明，高表达RIG-I的样本与IFN-α反应以及抗肿瘤免疫细胞（尤其是CD8+T细胞）的富集呈正相关。此外，敲低RIG-I的表达可有效降低CRC细胞中IFN-α诱导的细胞死亡、STAT1磷酸化和CXCL10/11表达。最后，一项体内研究表明，RIG-I基因敲除组中CD3+CD8+T细胞的浸润显著减少。动物模型进一步证实，IFN-α联合抗PD-1治疗诱导的肿瘤生长抑制依赖于RIG-I的表达。
RIG-I是CRC免疫疗法中一个有前景的生物标志物，为联合免疫疗法提供了一个新概念。
