Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
The Third Clinical College, Southern Medical University, Guangzhou, People's Republic of China.
Reprod Sci. 2023 Aug;30(8):2468-2480. doi: 10.1007/s43032-023-01188-x. Epub 2023 Feb 9.
There was accumulating evidence indicating that tertiary lymphoid structures (TLSs) were strongly associated with improved survival and clinical outcome in several solid tumors. In this study, we intended to assess the presence of TLSs and their potential clinical significance in high-grade serous ovarian cancer (HGSOC). TCGA (The Cancer Genome Atlas) cohort included RNA-seq data of 376 HGSOC patients, of which 74 patients included available hematoxylin-eosin (H&E) sections; GEO (Gene Expression Omnibus) cohort, GSE140082, included microarray data of 212 HGSOC patients. TLSs were counted by pathological sections, and the relative abundance of TLSs was assessed by the unsupervised consensus clustering of 12-chemokine transcriptome signatures. The potential associations between TLSs and clinical prognosis, tumor microenvironment (TME), and immunotherapy response of HGSOC were further performed based on transcriptome data. In the H&E sections of HGSOC, TLSs were predominantly located in the stroma and invasive margin of the tumor. Pathological counting results suggested that the expression of 12 chemokines was significantly higher in samples abundant with TLSs than that in the lack of TLSs. Consensus clustering of both TCGA and GEO cohorts divided HGSOC patients into two clusters with different TLSs abundance: low- and high-TLSs. Based on transcriptome analysis, the high-TLS cluster was characterized by better clinical prognosis, a higher degree of immune infiltration, more biological pathways, higher tumor mutational burden score, and higher expression of immune checkpoints. In conclusion, TLSs strongly correlated with the immune-responsive microenvironment and remained a favorable prognostic factor independent of other clinical characteristics in HGSOC. The presence of TLSs was also associated with a potentially favorable response to immune checkpoint blockade (ICB) therapy in HGSOC.
有越来越多的证据表明，三级淋巴结构（TLS）与几种实体瘤的生存和临床结局改善密切相关。在这项研究中，我们旨在评估 TLS 在高级别浆液性卵巢癌（HGSOC）中的存在及其潜在的临床意义。TCGA（癌症基因组图谱）队列包括 376 例 HGSOC 患者的 RNA-seq 数据，其中 74 例患者包含可供使用的苏木精-伊红（H&E）切片；GEO（基因表达综合数据库）队列，GSE140082，包括 212 例 HGSOC 患者的微阵列数据。通过病理切片计数 TLS，并通过 12 种趋化因子转录组特征的无监督共识聚类评估 TLS 的相对丰度。基于转录组数据，进一步研究了 TLS 与 HGSOC 的临床预后、肿瘤微环境（TME）和免疫治疗反应之间的潜在关联。在 HGSOC 的 H&E 切片中，TLS 主要位于肿瘤的基质和侵袭边缘。病理计数结果表明，TLS 丰富的样本中 12 种趋化因子的表达明显高于缺乏 TLS 的样本。TCGA 和 GEO 队列的共识聚类将 HGSOC 患者分为两个具有不同 TLS 丰度的聚类：低 TLS 聚类和高 TLS 聚类。基于转录组分析，高 TLS 聚类的临床预后较好，免疫浸润程度较高，生物学途径较多，肿瘤突变负担评分较高，免疫检查点表达较高。总之，TLS 与免疫反应性微环境密切相关，在 HGSOC 中是独立于其他临床特征的有利预后因素。TLS 的存在也与 HGSOC 中免疫检查点阻断（ICB）治疗的潜在有利反应相关。
