Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USA; UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA; Division of Hematology and Oncology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Cancer Cell. 2024 Nov 11;42(11):1864-1881.e5. doi: 10.1016/j.ccell.2024.09.007. Epub 2024 Oct 10.
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.
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腔，这突出表明需要了解 HGSOC 部位的抗肿瘤免疫。通过空间分析，我们发现卵巢肿瘤中的三级淋巴结构 (TLS) 不如输卵管或大网膜肿瘤中的 TLS 发达。我们揭示了跨一系列淋巴结构的转录差异，表明当免疫细胞存在于更发达的 TLS 中时，其活性会增加，并从 HGSOC 肿瘤中产生预后的、空间衍生的 TLS 特征。我们研究了 TLS 附近的基质，并评估了正常间充质干细胞 (nMSC) 如何可能支持 B 细胞功能和 TLS，这与癌症诱导的间充质干细胞 (CA-MSC) 相反，后者否定了我们的 TLS 特征的预后益处，这表明促肿瘤性基质可能会限制 TLS 的形成。
