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
HTLV-1 感染对结直肠癌临床病理特征及肿瘤免疫微环境的影响
英文原题：Impact of HTLV-1 infection on clinicopathological characteristics and tumour immune microenvironment in colorectal cancer.
查看英文原题
Impact of HTLV-1 infection on clinicopathological characteristics and tumour immune microenvironment in colorectal cancer.
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中文摘要
近年来抗癌治疗的进展表明，肿瘤免疫微环境在肿瘤进展和抗癌治疗耐药中具有重要意义。本研究调查了在人类T细胞白血病病毒1型（HTLV-1）携带者高度流行地区单一机构切除的180例原发性结直肠癌（CRC）组织。在这180例中，鉴定出35例HTLV-1携带者。与非携带者相比，HTLV-1携带者的CRC患者年龄显著更大（平均年龄：76.9 vs. 72.7岁，P = 0.0341），淋巴结转移发生率更低（pN0：91% vs. 65%，P = 0.0085），肿瘤分期更低（III期或IV期：11% vs. 36%，P = 0.0117）。HTLV-1携带者倾向于显示较低的复发发生率，尽管差异不显著（P = 0.2272）。叉头框P3阳性调节性T细胞（Tregs）的密度在HTLV-1携带者中显著更高（中位密度：132 vs. 89 cells/mm 2，P = 0.0051）。原位杂交显示HTLV-1碱性亮氨酸拉链因子阳性细胞，可能代表位于癌巢周围间质中的淋巴细胞。
我们的发现表明，在感染HTLV-1的CRC患者中，淋巴结转移受到显著抑制。由于据报道HTLV-1感染会损害Tregs的免疫抑制功能，因此在HTLV-1携带者的CRC患者中，抗癌免疫反应可能增强。
展开英文摘要原文
Recent advances in anti-cancer therapy have indicated the significance of the tumour immune microenvironment in tumour progression and resistance to anti-cancer therapy.
This study investigated primary colorectal cancer (CRC) tissues resected from 180 cases in a single institute in a region highly endemic for human T-cell leukaemia virus type 1 (HTLV-1) carriers. Among those 180 cases, 35 HTLV-1 carriers were identified. CRC patients who were HTLV-1 carriers were significantly older (mean age: 76. 9 vs. 72. 7 years, P = 0. 0341), with a lower incidence of lymph node metastases (pN0: 91% vs. 65%, P = 0. 0085), and lower tumour stages (stage III or IV: 11% vs.
36%, P = 0. 0117) compared to non-carriers. HTLV-1 carriers tended to show a lower incidence of relapse, although the difference was not significant (P = 0. 2272). The density of forkhead box P3-positive regulatory T cells (Tregs) was significantly higher in HTLV-1 carriers (median density: 132 vs. 89 cells/mm 2 , P = 0. 0051). In situ hybridisation showed cells positive for HTLV-1 basic leucine zipper factor, likely representing lymphocytes located in stroma around the cancer nest.
Our findings indicate that lymph node metastasis was significantly suppressed in CRC patients infected with HTLV-1. Since HTLV-1 infection reportedly impairs the immunosuppressive functions of Tregs, anti-cancer immune responses are potentially enhanced in CRC patients who are HTLV-1 carriers.
论文信息
- 作者
- Yamada R、Arima K、Yano H、Fujiwara Y、Yamashita K、Kanemitsu K、Hanada N、Yasunaga JI
- 第一作者单位
- Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan.Japan
- 通讯作者单位
- Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan. ycomo@kumamoto-u.ac.jp.Japan
- 期刊
- Virchows Archiv : an international journal of pathology2025 Oct
- 原文标识
- PubMed 40111448 · DOI 10.1007/s00428-025-04074-w
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