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
猪黑色素瘤的自发消退：肿瘤浸润性 T 细胞和 NK 细胞的作用
英文原题：Spontaneous Regression of Swine Melanoma: The Role of Tumour-infiltrating T and NK Cells.
查看英文原题
Spontaneous Regression of Swine Melanoma: The Role of Tumour-infiltrating T and NK Cells.
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研究概要
细胞毒性 T 细胞是 10-32 周龄 MeLiM 黑色素瘤中发现的肿瘤浸润免疫细胞中最丰富的群体，可能导致了黑色素瘤细胞的破坏。此外，主要以细胞毒性 T 细胞为代表的特异性（适应性）免疫反应的发展似乎对猪黑色素瘤的成功 SR 至关重要。
研究思路结论见上方概要
背景
黑色素瘤是一种缺乏有效疗法的皮肤癌，具有高免疫原性，且大多表现为部分自发消退（SR）。SR的确切机制仍未被充分了解；因此，有必要使用动物黑色素瘤模型来揭示SR期间的免疫学过程。
方法
收集了来自同一动物的皮肤黑色素瘤样本（n=57）和外周血样本（n=57）。使用3、4、6、8、10、12、20和32周龄的携带黑色素瘤的Libechov小型猪（MeLiM），并通过流式细胞术分析样本以检测免疫细胞亚群。
结果
在6-8周龄以及随后12周龄时，黑色素瘤样本中CD3-CD8+（NK）细胞的比例高于血液样本。在10-32周龄猪中，黑色素瘤样本中CD4+CD8+（效应/记忆T辅助）细胞和CD4-CD8+（细胞毒性T和NK）细胞群体也较血液样本增加。黑色素瘤样本中CD4-CD8+细胞的比例随后持续增加至第32周。相反，在6-32周龄动物中，黑色素瘤样本中CD4+CD8-（初始T辅助）细胞的比例低于血液样本。
展开英文摘要原文
MATERIALS AND METHODS
Skin melanoma samples (n=57) and peripheral blood samples (n=57) from the same animals were collected. Melanoma-bearing Libechov Minipigs (MeLiM) aged 3, 4, 6, 8, 10, 12, 20, and 32 weeks were used, and samples were analysed by flow cytometry for detection of immune cell subpopulations.
RESULTS
The proportion of CD3-CD8+ (NK) cells in melanoma samples was found to be higher compared to blood samples at 6-8 weeks of age and then at 12 weeks of age. The population of CD4+CD8+ (effector/memory T helper) cells and CD4-CD8+ (cytotoxic T and NK) cells was also increased in melanoma compared to blood samples in 10-32-week-old pigs. The proportion of CD4-CD8+ cells in melanoma samples, then augmented until the 32 nd week. On the contrary, the proportion of CD4+CD8- (naive T helper) cells was lower in melanoma samples versus blood samples in 6-32-week-old animals.
CONCLUSION
Cytotoxic T cells were the most abundant population of tumour infiltrating immune cells found in MeLiM melanomas of animals aged 10-32 weeks, probably causing the destruction of melanoma cells. Furthermore, the development of specific (adaptive) immune response represented mainly by cytotoxic T cells seems to be crucial for the successful SR of porcine melanoma.
论文信息
- 作者
- Planska D、Horak V
- 单位
- Kralovske Vinohrady University Hospital, Prague, Czech Republic; planskad@seznam.cz.Czechia
- 期刊
- Anticancer research2023 Feb
- 原文标识
- PubMed 36697105 · DOI 10.21873/anticanres.16199