Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Division of Hematology and Cellular Therapy, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Sci Adv. 2024 Apr 19;10(16):eadk8805. doi: 10.1126/sciadv.adk8805. Epub 2024 Apr 17.
High-grade serous ovarian carcinoma (HGSOC), the deadliest form of ovarian cancer, is typically diagnosed after it has metastasized and often relapses after standard-of-care platinum-based chemotherapy, likely due to advanced tumor stage, heterogeneity, and immune evasion and tumor-promoting signaling from the tumor microenvironment. To understand how spatial heterogeneity contributes to HGSOC progression and early relapse, we profiled an HGSOC tissue microarray of patient-matched longitudinal samples from 42 patients. We found spatial patterns associated with early relapse, including changes in T cell localization, malformed tertiary lymphoid structure (TLS)-like aggregates, and increased podoplanin-positive cancer-associated fibroblasts (CAFs). Using spatial features to compartmentalize the tissue, we found that plasma cells distribute in two different compartments associated with TLS-like aggregates and CAFs, and these distinct microenvironments may account for the conflicting reports about the role of plasma cells in HGSOC prognosis.
高级别浆液性卵巢癌（HGSOC）是最致命的卵巢癌形式，通常在转移后才被诊断出来，并且在标准护理铂类化疗后经常复发，这可能是由于晚期肿瘤分期、异质性以及肿瘤微环境中的免疫逃逸和促进肿瘤的信号。为了了解空间异质性如何促进 HGSOC 的进展和早期复发，我们对来自 42 名患者的患者匹配的纵向样本的 HGSOC 组织微阵列进行了分析。我们发现了与早期复发相关的空间模式，包括 T 细胞定位的变化、畸形的三级淋巴结构 (TLS)样聚集以及更多的 podoplanin 阳性癌相关成纤维细胞 (CAFs)。利用空间特征对组织进行分区，我们发现浆细胞分布在与 TLS 样聚集和 CAFs 相关的两个不同的区室中，这些不同的微环境可能解释了关于浆细胞在 HGSOC 预后中的作用的相互矛盾的报告。
