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:The effect of neoadjuvant radiotherapy on immune cell infiltrates in myxofibrosarcoma.
The effect of neoadjuvant radiotherapy on immune cell infiltrates in myxofibrosarcoma.
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常规 nRT 与 MFS 中细胞毒性和辅助性 T 细胞浸润减少及 NK 细胞存在增加相关。这些结果提示,常规 nRT 减轻了 MFS 肿瘤的炎症特征。
黏液纤维肉瘤(MFS)是软组织肉瘤的一种亚型,其局部治疗包括新辅助放疗(nRT)后手术。nRT对MFS肿瘤免疫微环境的影响尚未被探索。
回顾性收集了31例MFS患者的配对nRT前活检和nRT后手术样本。使用多重免疫组化(mIHC)定量了肿瘤内T细胞、细胞毒性T细胞、调节性T细胞、辅助性T细胞、B细胞和自然杀伤(NK)细胞的密度以及程序性死亡配体1的表达。比较了nRT前后样本之间的mIHC标志物密度,并评估了它们与临床病理特征和患者结局的关联。
mIHC标志物密度在nRT前后均存在显著的患者间异质性。nRT后观察到细胞毒性T细胞密度显著降低{nRT前205[四分位距(IQR)674]对nRT后58(IQR 205),P = 0.030},辅助T细胞密度显著降低[nRT前220(IQR 343)对nRT后74(IQR 110),P = 0.011],同时NK细胞浸润增加[nRT前2(IQR 8)对nRT后7(IQR 16),P = 0.050]。nRT前后测量的mIHC标志物密度及其随时间的变化与患者结局之间均无统计学显著关联。
Myxofibrosarcoma (MFS) is a subtype of soft-tissue sarcoma for which local treatment includes neoadjuvant radiotherapy (nRT) followed by surgery. The impact of nRT on the MFS tumor immune microenvironment remains unexplored.
Paired pre-nRT biopsy and post-nRT surgery samples from 31 MFS patients were retrospectively collected. The intratumoral density of T cells, cytotoxic T cells, regulatory T cells, helper T cells, B cells and natural killer (NK) cells and expression of programmed death-ligand 1 were quantified using multiplex immunohistochemistry (mIHC). mIHC marker densities were compared between pre- and post-nRT samples, and their associations with clinicopathological characteristics and patient outcomes were assessed.
There was substantial interpatient heterogeneity in mIHC marker densities, both pre- and post-nRT. A significant reduction in cytotoxic T cell {205 [interquartile range (IQR) 674] pre-nRT versus 58 (IQR 205) post-nRT, P = 0.030} and helper T cell [220 (IQR 343) pre-nRT versus 74 (IQR 110) post-nRT, P = 0.011] densities, alongside an increase in NK cell [2 (IQR 8) pre-nRT versus 7 (IQR 16) post-nRT, P = 0.050] infiltration, was observed following nRT. There were no statistically significant associations between mIHC marker densities measured before or after nRT, or their changes over time, and patient outcomes.
Conventional nRT is associated with reduced cytotoxic and helper T cell infiltration and increased presence of NK cells in MFS. These results suggest that conventional nRT reduces inflammatory aspects of MFS tumors.
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