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SOX17 在肿瘤穿透血管中的表达与肿瘤基质龛中 CD8 T 细胞浸润的关系。

SOX17 expression in tumor-penetrating vessels in relation to CD8 T-cell infiltration in cancer stroma niches.

机构信息

Department of General Thoracic Surgery, Gifu University Hospital, Gifu, Japan.

Department of Pathology and Translational Research, Gifu Medical School of Medicine, Gifu, Japan.

出版信息

Thorac Cancer. 2024 Nov;15(32):2319-2326. doi: 10.1111/1759-7714.15464. Epub 2024 Oct 9.

Abstract

INTRODUCTION

Sex-determining region Y-related high-mobility group box 17 protein (SOX17), a proangiogenic transcription factor, is specifically expressed in tumor endothelial cells (TECs) of implanted Lewis lung carcinoma. However, the expression profile of SOX17 is largely unknown in human lung cancer. We aimed to elucidate SOX17 expression in cancer cells and the tumor microenvironment of lung adenocarcinoma.

METHODS

In the present study, we examined SOX17 expression in whole-tissue specimens of 83 lung adenocarcinomas by immunohistochemistry.

RESULTS

SOX17 immunoreactivity was minimal in lung adenocarcinoma cells, except in five non-mucinous adenocarcinomas in situ. SOX17 was also expressed in cultured A549 lung adenocarcinoma cells, which is widely used as a model of malignant alveolar type II epithelial cells. Notably, SOX17 immunoreactivity was found in endothelial cells of tumor-penetrating vessels in 19 of 83 lung adenocarcinoma tissue specimens, with statistical significance to stromal infiltration of CD8 T cells (p < 0.01) but was not associated with the number of tertiary lymph nodes. Although not statistically significant, SOX17 immunoreactivity was related to favorable patient outcomes.

CONCLUSION

Our findings indicate that SOX17 might play a pleiotropic role in lung adenocarcinoma in cancer cells and stromal niches. SOX17-mediated CD8 T-cell-rich tumor microenvironment might attract interest in improving the effect of cancer immunotherapy.

摘要

简介

性别决定区 Y 相关高迁移率族 box 17 蛋白(SOX17)是一种促血管生成转录因子,特异性表达于植入性 Lewis 肺癌的肿瘤内皮细胞(TEC)中。然而,SOX17 在人类肺癌中的表达谱尚不清楚。我们旨在阐明肺腺癌中 SOX17 在癌细胞和肿瘤微环境中的表达情况。

方法

本研究通过免疫组织化学法检测了 83 例肺腺癌全组织标本中 SOX17 的表达情况。

结果

SOX17 在肺腺癌细胞中的表达很少,除了原位非黏液性腺癌的 5 例。SOX17 也在培养的 A549 肺腺癌细胞中表达,该细胞常被用作恶性肺泡 II 型上皮细胞的模型。值得注意的是,在 83 例肺腺癌组织标本中的 19 例中发现了穿透肿瘤的血管内皮细胞的 SOX17 免疫反应性,与 CD8 T 细胞的基质浸润有统计学意义(p<0.01),但与三级淋巴节点的数量无关。虽然没有统计学意义,但 SOX17 免疫反应性与患者预后良好相关。

结论

我们的研究结果表明,SOX17 可能在肺腺癌的癌细胞和基质龛中发挥多种作用。SOX17 介导的富含 CD8 T 细胞的肿瘤微环境可能会引起人们对改善癌症免疫治疗效果的兴趣。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1af/11554551/34157e93667e/TCA-15-2319-g004.jpg

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