Zhang Yanhui, Ju Baohui, Cheng Runfen, Ding Tingting, Wu Jianghua
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Department of Gynecology and Obstetrics, the Second Hospital of Tianjin Medical University, Tianjin, China.
Hum Pathol. 2024 Dec;154:105704. doi: 10.1016/j.humpath.2024.105704. Epub 2024 Dec 9.
The immune subtypes of the tumor microenvironment in endometrial cancer (EC), associated with different molecular classifications, warrant further investigation to guide EC immunotherapy strategies. This study focused on programmed death-ligand 1 (PD-L1) expression (Clone SP263) and immune cell (IC) markers (CD3, CD8, CD68, CD20, CD21) in 110 EC cases. In this cohort, the molecular subtype distribution was: POLE mutation (POLEmut) 7.3% (8/110), mismatch repair-deficient (MMRd) 21.8% (24/110), p53 abnormal (p53abn) 14.5% (16/110), and non-specific molecular profile (NSMP) 56.4% (62/110). NSMP subtypes exhibited the lowest PD-L1+ cell densities and scores. POLEmut and MMRd subtypes showed higher IC densities, while p53abn and NSMP subtypes had lower IC densities and fewer tertiary lymphoid structures (TLS). Integrative analysis of immune subtypes with PD-L1 and CD8 tumor infiltrating lymphocytes (TILs) revealed 62.5% of POLEmut and 45.8% of MMRd cases as TIME type Ⅰ (PD-L1 & CD8). Conversely, p53abn and NSMP cases were more heterogeneous, with 37.5% of p53abn cases in TIME type Ⅲ (PD-L1 & CD8) and 41.9% of NSMP cases in TIME type Ⅱ (PD-L1 & CD8). Higher CD8 T cell density was a prognostic marker for disease-free survival in EC, including within NSMP (p < 0.05). In summary, the four WHO molecular subtypes of EC exhibit distinct TIME subtypes, complementing molecular classification and providing insights for optimizing EC immunotherapy strategies.
子宫内膜癌（EC）肿瘤微环境的免疫亚型与不同的分子分类相关，有必要进一步研究以指导EC免疫治疗策略。本研究聚焦于110例EC病例中的程序性死亡配体1（PD-L1）表达（克隆号SP263）和免疫细胞（IC）标志物（CD3、CD8、CD68、CD20、CD21）。在该队列中，分子亚型分布为：POLE突变（POLEmut）7.3%（8/110），错配修复缺陷（MMRd）21.8%（24/110），p53异常（p53abn）14.5%（16/110），以及非特异性分子谱（NSMP）56.4%（62/110）。NSMP亚型的PD-L1+细胞密度和评分最低。POLEmut和MMRd亚型显示出较高的IC密度，而p53abn和NSMP亚型的IC密度较低且三级淋巴结构（TLS）较少。对免疫亚型与PD-L1和CD8肿瘤浸润淋巴细胞（TILs）的综合分析显示，62.5%的POLEmut病例和45.8%的MMRd病例为TIMEⅠ型（PD-L1 & CD8）。相反，p53abn和NSMP病例的异质性更高，37.5%的p53abn病例为TIMEⅢ型（PD-L1 & CD8），41.9%的NSMP病例为TIMEⅡ型（PD-L1 & CD8）。较高的CD8 T细胞密度是EC无病生存的预后标志物，包括在NSMP中（p < 0.05）。总之，EC的四种WHO分子亚型表现出不同的TIME亚型，补充了分子分类，并为优化EC免疫治疗策略提供了见解。
