美国匹兹堡大学Tullia C. Bruno等研究人员合作发现，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调控。该项研究成果于2024年10月10日在线发表在《癌细胞》杂志上。

通过空间分析，研究人员发现卵巢肿瘤中的三级淋巴结构（TLS）发育，不如输卵管或网膜肿瘤中的TLS完善。研究人员揭示了不同淋巴结构中的转录差异，展示了免疫细胞活性在更发育完善的TLSs中增强，并从高级别浆液性卵巢癌（HGSOC）肿瘤中生成了，具有预后意义的空间TLS特征。

研究人员揭示了TLS邻近基质，评估了正常间充质干细胞（nMSC）如何支持B细胞功能和TLS的形成。相反，经过癌症驯化的MSC（CA-MSC）消除了TLS特征的预后优势，表明促肿瘤基质可能会限制TLS的形成。

研究人员表示，大多数HGSOC起源于输卵管，但会扩散至卵巢和腹膜腔，这凸显了理解HGSOC各部位抗肿瘤免疫的重要性。

附：英文原文

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

Author: 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

Issue&Volume: 2024-10-10

Abstract: 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.

DOI: 10.1016/j.ccell.2024.09.007

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00355-6