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肿瘤内 T 细胞的空间计算与胰腺癌患者的生存相关。

Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer.

机构信息

Department of Cancer Biology, Metastasis Research Center, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Nat Commun. 2017 Apr 27;8:15095. doi: 10.1038/ncomms15095.

Abstract

The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section. We report a heterogeneous population of infiltrating T lymphocytes. Spatial distribution of cytotoxic T cells in proximity to cancer cells correlates with increased overall patient survival. Collagen-I and αSMA fibroblasts do not correlate with paucity in T-cell accumulation, suggesting that PDAC desmoplasia may not be a simple physical barrier. Further exploration of this technology may improve our understanding of how specific stromal composition could impact T-cell activity, with potential impact on the optimization of immune-modulatory therapies.

摘要

胰腺导管腺癌 (PDAC) 免疫组成的确切性质和动态在很大程度上仍然未知。细胞外基质纤维化被认为使 PDAC 免疫发生极化。因此,全面评估细胞外基质纤维化元素和 T 细胞浸润的组成和分布对于阐明它们的作用是必要的。在这里,我们开发了一种新的计算成像技术,用于同时评估 8 种不同的标志物,从而能够在同一切片上对不同群体进行空间分析。我们报告了浸润性 T 淋巴细胞的异质性群体。接近癌细胞的细胞毒性 T 细胞的空间分布与患者总生存率的提高相关。Ⅰ型胶原和αSMA 成纤维细胞与 T 细胞积累的稀少无关,这表明 PDAC 细胞外基质纤维化可能不是简单的物理屏障。进一步探索这项技术可能有助于我们了解特定基质组成如何影响 T 细胞活性,并可能对免疫调节治疗的优化产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/5414182/403b2f08891f/ncomms15095-f1.jpg

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