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:Comparison and analysis of the immune landscape at the tumour invasion front in patients with pMMR/MSI-H and pMMR/MSS colorectal cancer.
Comparison and analysis of the immune landscape at the tumour invasion front in patients with pMMR/MSI-H and pMMR/MSS colorectal cancer.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
pMMR/MSI-H 与 pMMR/MSS CRC 在肿瘤浸润前沿的免疫细胞浸润和分布存在显著差异。dMMR CRC 患者肿瘤浸润前沿 CD8⁺ T 细胞和 CD56 bright⁺细胞浸润较高,可能部分解释了其对免疫治疗更好的应答。然而,这些发现需要在更大队列中验证。
本研究旨在比较和分析错配修复正常(pMMR)与错配修复缺陷(dMMR)的结直肠癌(CRC)患者肿瘤浸润前沿的免疫景观。
共纳入51例CRC患者,包括32例pMMR患者和19例dMMR患者。采用免疫组化、荧光PCR和毛细管电泳检测MLH1、PMS2、MSH2和MSH6蛋白的表达状态,以识别pMMR/MSI-H和pMMR/MSS患者。采用多重免疫荧光技术对肿瘤浸润前沿的免疫细胞进行染色和分析。
在dMMR CRC患者中,肿瘤浸润前沿的CD8⁺ T细胞比例显著高于pMMR患者(26.84% ± 3.17% vs. 6.29% ± 1.62%,p < 0.001),而CD4⁺ T细胞比例显著较低(19.02% ± 2.81% vs. 37.71% ± 3.52%,p < 0.001)。关于NK细胞,dMMR患者肿瘤浸润前沿的CD56 bright⁺细胞比例显著高于pMMR患者(6.69% ± 1.04% vs. 1.93% ± 0.48%,p < 0.001)。两组之间肿瘤浸润前沿NK细胞总数无显著差异。
This study aims to compare and analyse the immune landscape at the tumour invasion front in patients with colorectal cancer (CRC) with proficient mismatch repair (pMMR) and deficient mismatch repair (dMMR).
A total of 51 patients with CRC were included, comprising 32 patients with pMMR and 19 patients with dMMR. Immunohistochemistry, fluorescence PCR and capillary electrophoresis were used to detect the expression status of MLH1, PMS2, MSH2 and MSH6 proteins to identify patients with pMMR/MSI-H and pMMR/MSS. Multiplex immunofluorescence technology was employed to stain and analyse immune cells at the tumour invasion front.
In patients with dMMR CRC, the proportion of CD8⁺ T cells at the tumour invasion front was significantly higher than that in patients with pMMR (26.84% ± 3.17% vs. 6.29% ± 1.62%, p < 0.001), whereas the proportion of CD4⁺ T cells was significantly lower (19.02% ± 2.81% vs. 37.71% ± 3.52%, p < 0.001). Regarding NK cells, the proportion of CD56 bright⁺ cells at the tumour invasion front in patients with dMMR was significantly higher than that in patients with pMMR (6.69% ± 1.04% vs. 1.93% ± 0.48%, p < 0.001). There was no significant difference in the total number of NK cells at the tumour invasion front between the two groups.
There are significant differences in the infiltration and distribution of immune cells at the tumour invasion front between pMMR/MSI-H and pMMR/MSS CRC. The higher infiltration of CD8⁺ T cells and CD56 bright⁺ cells at the tumour invasion front in patients with dMMR CRC may partly explain their better response to immune therapy. However, these findings require validation in larger cohorts.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
MEMBER ACCOUNT
登录成功会直接打开下一页。