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:Relationship between stromal regulatory T cells and the response to neoadjuvant chemotherapy for locally advanced rectal cancer.
Relationship between stromal regulatory T cells and the response to neoadjuvant chemotherapy for locally advanced rectal cancer.
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间质细胞区域中 Treg 浸润低可能是局部晚期直肠癌患者对新辅助化疗反应良好的标志。
除抗癌药物的直接作用外,抗癌治疗的疗效还取决于宿主免疫功能。本研究探讨了术前化疗的缩减率及组织学反应是否与直肠原发肿瘤周围的免疫微环境相关。
2012年至2014年,65例患者接受了术前化疗后切除,所有患者均进行了回顾性分析。分别通过免疫组化检测CD3、CD8和FoxP3作为T淋巴细胞、细胞毒性T淋巴细胞和调节性T淋巴细胞(Treg)的标志物。研究了TIL(肿瘤浸润淋巴细胞)组成与肿瘤缩小率及新辅助化疗组织学反应之间的相关性。
平均肿瘤缩小率为41.5% ± 18.8%。根据RECIST标准,47例患者(72.3%)达到部分缓解(PR),1例患者(1.5%)达到完全缓解(CR)。8例患者(12.3%)显示组织学2级反应,2例(3.1%)显示3级反应。多因素分析表明,间质细胞区域Treg低浸润与达到PR或CR显著相关[比值比(OR)7.69;95%置信区间(CI)1.96-33.33;p < 0.01],也与组织学2级或3级反应显著相关(OR 11.11;95% CI 1.37-98.04;p = 0.02)。
In addition to the direct power of anticancer drugs, the effectiveness of anticancer therapy depends on the host immune function. The present study investigated whether or not the reduction rate and histological response of preoperative chemotherapy were related to the immune microenvironment surrounding a primary tumor of the rectum.
Sixty-five patients received preoperative chemotherapy followed by resection from 2012 to 2014; all of these patients were retrospectively analyzed. CD3, CD8, and FoxP3 were immunohistochemically examined as markers for T lymphocytes, cytotoxic T lymphocytes, and regulatory T lymphocytes (Treg), respectively. The correlation between the tumor-infiltrating lymphocyte composition and the tumor reduction rate and histological response to neoadjuvant chemotherapy was investigated.
The average tumor reduction rate was 41.5% ± 18.8%. According to RECIST, 47 patients (72.3%) achieved a partial response (PR), and 1 patient (1.5%) achieved a complete response (CR). Eight patients (12.3%) showed a grade 2 histological response, and 2 (3.1%) showed a grade 3 response. A multivariate analysis demonstrated that a low Treg infiltration in stromal cell areas was significantly associated with the achievement of a PR or CR [odds ratio (OR) 7.69; 95% confidence interval (CI) 1.96-33.33; p < 0.01] and a histological grade 2 or 3 response (OR 11.11; 95% CI 1.37-98.04; p = 0.02).
A low Treg infiltration in the stromal cell areas may be a marker of a good response to neoadjuvant chemotherapy in patients with locally advanced rectal cancer.
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