高级别浆液性卵巢癌中三级淋巴结构的活性受部位、基质和细胞相互作用的影响

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2024-10-10 DOI:10.1016/j.ccell.2024.09.007

Ian P. MacFawn, Grant Magnon, Grace Gorecki, Sheryl Kunning, Rufiaat Rashid, Medard Ernest Kaiza, Huda Atiya, Ayana T. Ruffin, Sarah Taylor, T. Rinda Soong, Riyue Bao, Lan G. Coffman, Tullia C. Bruno

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引用次数: 0

摘要

大多数高级别浆液性卵巢癌（HGSOC）起源于输卵管，但会扩散到卵巢和腹膜腔，因此需要了解HGSOC不同部位的抗肿瘤免疫。通过空间分析，我们发现卵巢肿瘤内的三级淋巴结构（TLS）与输卵管或网膜肿瘤内的三级淋巴结构相比发育较差。我们揭示了一系列淋巴结构的转录差异，证明了免疫细胞在较发达的三级淋巴结构中的活性会增加，并从 HGSOC 肿瘤中得出了一个预后、空间衍生的三级淋巴结构特征。我们研究了TLS邻近基质，并评估了正常间充质干细胞间充质干细胞（nMSCs）如何支持B细胞功能和TLS，这与癌症教育间充质干细胞（CA-MSCs）相反，后者否定了我们TLS特征的预后益处，这表明促肿瘤基质可能会限制TLS的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions

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The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions

Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLSs) within ovarian tumors are less developed compared with TLSs in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLSs and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.