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
β2 微球蛋白阳性肿瘤细胞和 CD8 阳性淋巴细胞与新辅助治疗后结直肠癌切除术后的预后相关
英文原题：Beta-2-microglobulin positive tumor cells and CD8 positive lymphocytes are associated with outcome in post-neoadjuvant colorectal cancer resections.
查看英文原题
Beta-2-microglobulin positive tumor cells and CD8 positive lymphocytes are associated with outcome in post-neoadjuvant colorectal cancer resections.
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中文摘要
局部晚期结直肠癌采用新辅助治疗（NAT），已被证明会改变肿瘤的特征，包括大小、淋巴结检出数和组织学分级。我们试图探究NAT对免疫微环境的影响。
我们比较了190例接受NAT治疗的结直肠腺癌患者与未接受NAT治疗的患者（n = 926）。我们评估了临床病理和分子因素，并对组织芯片进行了免疫组化及定量分析，检测HLA I/II类蛋白、β2-微球蛋白（B2M）、CD8、CD163、LAG3、PD-L1和FoxP3。NAT组患者比非NAT组更年轻（60.9 vs 67.9，p < 0.001），且男性比例更高（59.5% vs. 47.9%，p = 0.004）。NAT组肿瘤更小（3.5 vs 4.7 cm，p < 0.001），高级别比例更低（6.5% vs. 16.2%，p = 0.001），直肠部位更常见（68.9% vs. 6.6%，p < 0.001），且淋巴结检出数更低（p = 0.002）；然而，壁外静脉侵犯、神经周围侵犯和AJCC 3-4期疾病的发生率无差异。NAT组中CD8阳性免疫细胞显著更低（p = 0.011）。在NAT组和非NAT组中，高数量的CD8+细胞和肿瘤细胞中B2M的高表达均显示出显著的生存获益。NAT与免疫低肿瘤环境相关。CD8+细胞和肿瘤B2M表达可能有助于识别NAT后免疫高肿瘤的亚群。这种识别可能有助于确定可能从结直肠癌保守治疗中获益的患者。
展开英文摘要原文
Locally advanced colorectal cancers are treated with neoadjuvant therapy (NAT), which has been shown to alter the characteristics of the tumor including size, lymph node yield, and histologic grade.
We seek to interrogate the effect of NAT on the immune microenvironment.
We compared 190 patients with colorectal adenocarcinoma treated with NAT with those without NAT (n = 926).
We evaluated clinicopathologic and molecular factors and performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2M), CD8, CD163, LAG3, PD-L1, and FoxP3. Patients in the NAT group were younger (60. 9 vs 67. 9, p < 0. 001) and more often male (59. 5 vs. 47. 9, p = 0. 004) than those in the non-NAT group. Tumors in the NAT group were smaller (3. 5 vs 4. 7 cm, p < 0. 001), less often high grade (6. 5% vs. 16. 2%, p = 0. 001), more frequently in the rectum (68. 9% vs. 6. 6%, p < 0. 001) and associated with lower lymph node yields (p = 0.
002); however, the incidence of extramural venous invasion, perineural invasion, and AJCC stage 3-4 disease were not different. Immune cells positive for CD8 (p = 0. 011) were significantly lower in the NAT group. A high number of CD8 + cells and higher expression of B2M in tumor cells showed a significant survival benefit in both NAT and non-NAT group.
NAT is associated with an immune-low tumor environment. CD8 + cells and tumor B2M expression may help identify a subset of immune high-tumors following NAT. This identification could aid in determining patients who may benefit from conservative management of colorectal carcinomas.
论文信息
- 作者
- Lee SH、Pankaj A、Yilmaz O、Deshpande V、Yilmaz O
- 第一作者单位
- Department of Pathology, Boston Medical Center, Boston, MA, USA.United States
- 通讯作者单位
- Harvard Medical School, Boston, MA, USA; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: osmanhy@gmail.com.United States
- 期刊
- Human pathology2025 Jan
- 原文标识
- PubMed 39988058 · DOI 10.1016/j.humpath.2025.105737