Kaneta Akinao, Nakajima Shotaro, Mimura Kosaku, Kono Koji
Dept. of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine.
Gan To Kagaku Ryoho. 2022 Oct;49(10):1130-1132.
Deficient mismatch repair (dMMR)/microsatellite instability (MSI)-H colorectal cancer (CRC) has high immunogenicity. Although the cyclic GMP-AMP synthase( cGAS)-stimulator of interferon genes( STING) pathway activation has considerably contributed to the high number of CD8+ tumor-infiltrating lymphocytes (TILs), its role in dMMR/MSI-H CRC is largely unknown. In this study, we investigated the association between cGAS-STING expression and CD8+ TILs in CRC. Data analysis using the TCGA dataset CRC cohort showed that cGAS, STING, and CD8 gene expression levels were significantly higher in the MSI group. Immunohistochemistry examination of resected clinical CRC samples showed that cGAS-STING expression in tumor cells was high in the MSI CRC, and CD8+ TILs was also significantly infiltrated in the MSI group. Moreover, significant CD8+ TILs infiltration was observed in CRC with high cGAS and STING expression levels. The results suggest that dMMR/MSI -H CRC has maintained a high cGAS-STING expression, which may contribute to abundant CD8+ TILs.
错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）的结直肠癌（CRC）具有高免疫原性。尽管环磷酸鸟苷-腺苷酸合成酶（cGAS）-干扰素基因刺激因子（STING）途径的激活在大量CD8+肿瘤浸润淋巴细胞（TILs）的产生中起了很大作用，但其在dMMR/MSI-H CRC中的作用在很大程度上尚不清楚。在本研究中，我们调查了CRC中cGAS-STING表达与CD8+ TILs之间的关联。使用TCGA数据集CRC队列进行的数据分析显示，MSI组中cGAS、STING和CD8基因的表达水平显著更高。对切除的临床CRC样本进行免疫组织化学检查显示，MSI CRC中肿瘤细胞的cGAS-STING表达较高，并且MSI组中CD8+ TILs也有显著浸润。此外，在cGAS和STING表达水平高的CRC中观察到显著的CD8+ TILs浸润。结果表明，dMMR/MSI-H CRC维持了较高的cGAS-STING表达，这可能有助于大量CD8+ TILs的产生。
