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:CD8-positive lymphocyte infiltration as a marker of anti-tumor immune response in rectal cancer: pre- and post-neoadjuvant radiotherapy comparison.
CD8-positive lymphocyte infiltration as a marker of anti-tumor immune response in rectal cancer: pre- and post-neoadjuvant radiotherapy comparison.
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我们的研究强调,SCRT 和 LCRT 均显著增加 CD8+ TIL 计数和百分比,反映出直肠癌放疗后强烈的免疫激活,其中 SCRT 显示出更高的相对增幅,但在未调整分析中无统计学意义。在调整组织病理学变量后,SCRT 与 CD8+ T 细胞增幅更大独立相关。
抗肿瘤免疫由CD8+细胞毒性T淋巴细胞发挥,在肿瘤控制中起着至关重要的作用。因此,本研究旨在比较直肠癌患者在接受长程放疗(LCRT)或短程放疗(SCRT)前后CD8+TIL(肿瘤浸润淋巴细胞)(TILs)的数量。
本研究回顾性评估了2019年至2021年间接受新辅助放疗的直肠癌患者。对活检样本和手术样本进行免疫组化染色以计数CD8+ TIL。评估了治疗后与治疗前CD8+计数比值与治疗分组、组织病理学因素及治疗反应之间的关联。
共纳入34例患者,其中23例(67.6%)接受LCRT,11例(32.4%)接受SCRT。平均年龄为58.56 13.59岁。所有患者放疗后CD8+ TILs的数量和百分比均显著增加(P < 0.001)。两组均观察到CD8+ TILs增加,LCRT组治疗前后计数中位比值为2.77,SCRT组为3.1(P = 0.127)。在调整粘液性组织学、手术分级和病理分期后的广义线性多变量模型显示,与LCRT相比,SCRT与显著更高的治疗前后CD8+计数比值相关(P = 0.03)。
Antitumor immunity, exerted by CD8+ cytotoxic T lymphocytes, plays a vital role in tumor control. Therefore, the present study was conducted to compare the amount of CD8+ tumor-infiltrating lymphocytes (TILs) before and after either long- (LCRT) or short-course radiotherapy (SCRT) in rectal cancer.
This study retrospectively assessed rectal cancer patients treated by neoadjuvant radiotherapy between 2019 and 2021. Biopsy and surgical samples were subjected to immunohistochemical staining to count CD8+ TILs. The association between the post-to-pre-treatment CD8+ count ratio and treatment groups, histopathological factors, and response to treatment was assessed.
A total of 34 patients were included, with 23 (67.6 %) receiving LCRT and 11 (32.4 %) receiving SCRT. The mean age was 58.56 13.59 years. The number and percentage of CD8+ TILs increased significantly after radiotherapy in all patients (P < 0.001). An increase in CD8+ TILs was observed in both groups, with LCRT showing a median post-to-pre-treatment count ratio of 2.77 and SCRT showing 3.1 (P = 0.127). A generalized linear multivariate model adjusting for mucinous histology, surgical grade, and pathological stages revealed that SCRT was associated with a significantly higher post-to-pre-treatment CD8+ count ratio compared to LCRT (P = 0.03).
Our study highlights that both SCRT and LCRT significantly increase CD8+ TIL count and percentage, reflecting robust immune activation after radiotherapy in rectal cancer, with SCRT showing a higher relative increase, though not statistically significant in unadjusted analyses. After adjusting for histopathological variables, SCRT was independently associated with a greater increase in CD8+ T cells.
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