Westbom-Fremer Sofia, Tran Lena, Ebbesson Anna, Martin de la Fuente Laura, Jönsson Jenny-Maria, Kannisto Päivi, Veerla Srinivas, Hedenfalk Ingrid
Division of Oncology, Department of Clinical Sciences Lund, and Lund University Cancer Center, Lund University, Lund, Sweden.
Division of Obstetrics and Gynaecology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
Cancer Immunol Immunother. 2025 Jan 3;74(2):56. doi: 10.1007/s00262-024-03911-2.
Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (pMets) of HGSC. Whole H&E slides were scrutinized for mTLS and LA in a population-based cohort of 130 cases with stage III-IV HGSC. The immune cell tumor infiltration was evaluated with single chromogenic immunohistochemistry (IHC) on a tissue microarray (TMA) from the same cases. Selected whole slides (PT n = 11, pMet n = 10) of the cases most abundant in mTLS and LA were further investigated with multiplex IHC and immunofluorescence using digital image analysis (QuPath), to confirm TLS status and map the T and B lymphocyte subtypes. The results showed that mTLS were more common in pMets than in PTs but did not have an independent prognostic impact on overall or progression-free survival. The presence of mTLS correlated with intratumoral infiltration of CD8 cytotoxic T cells, FOXP3 regulatory T cells and PD-1 lymphocytes in pMets only. Although overall mTLS cell composition was similar between PTs and pMets, the outer zones of mTLS in PTs were more immune cell-rich. In conclusion, our results indicate differences in TLS presence and cellular elements between primary adnexal tumors and synchronous peritoneal metastases, which are important to consider when conducting studies of the immune environment in HGSC.
肿瘤微环境中的三级淋巴结构（TLS）在许多实体癌类型中具有预后益处。关于高级别浆液性输卵管卵巢癌（HGSC）中TLS的报道很少，其预后影响尚不清楚。我们研究了HGSC原发性附件肿瘤（PTs）和同步大网膜/腹膜转移灶（pMets）中的成熟TLS（mTLS）、未成熟TLS（iTLS）和淋巴样聚集物（LA）。在一个基于人群的130例III-IV期HGSC病例队列中，对全层苏木精-伊红（H&E）切片进行mTLS和LA的仔细检查。使用来自相同病例的组织微阵列（TMA）上的单显色免疫组织化学（IHC）评估免疫细胞肿瘤浸润情况。对mTLS和LA最丰富的病例的选定全层切片（PT n = 11，pMet n = 10），使用数字图像分析（QuPath）通过多重IHC和免疫荧光进一步研究，以确认TLS状态并绘制T和B淋巴细胞亚型图谱。结果显示，mTLS在pMets中比在PTs中更常见，但对总生存期或无进展生存期没有独立的预后影响。mTLS的存在仅与pMets中肿瘤内CD8细胞毒性T细胞、FOXP3调节性T细胞和PD-1淋巴细胞的浸润相关。尽管PTs和pMets之间mTLS的总体细胞组成相似，但PTs中mTLS的外层区域免疫细胞更丰富。总之，我们的结果表明原发性附件肿瘤和同步腹膜转移灶之间TLS的存在和细胞成分存在差异，这在进行HGSC免疫环境研究时是需要考虑的重要因素。
