Department of Gynecology, La Paz University Hospital, 28046 Madrid, Spain.
Research Institute "IdiPaz", La Paz University Hospital, 28046 Madrid, Spain.
Int J Mol Sci. 2023 Jul 28;24(15):12083. doi: 10.3390/ijms241512083.
the association between ovarian endometriosis (OE) and endometriosis-associated ovarian cancer (EAOC) is extensively documented, and misfunction of the immune system might be involved. The primary objective of this study was to identify and compare the spatial distribution of tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) in OE and EAOC. Secondary objectives included the analysis of the relationship between immunosuppressive populations and T-cell exhaustion markers in both groups.
TILs (CD3, CD4, and CD8) and macrophages (CD163) were assessed by immunochemistry. Exhaustion markers (PD-1, TIM3, CD39, and FOXP3) and their relationship with tumour-associated macrophages (CD163) were assessed by immunofluorescence on paraffin-embedded samples from = 43 OE and = 54 EAOC patients.
we observed a predominantly intraepithelial CD3+ distribution in OE but both an intraepithelial and stromal pattern in EAOC ( < 0.001). TILs were more abundant in OE ( < 0.001), but higher TILs significantly correlated with a longer overall survival and disease-free survival in EAOC ( < 0.05). CD39 and FOXP3 significantly correlated with each other and CD163 ( < 0.05) at the epithelial level in moderate/intense CD4 EAOC, whereas in moderate/intense CD8+, PD-1+ and TIM3+ significantly correlated ( = 0.009). Finally, T-cell exhaustion markers FOXP3-CD39 were decreased and PD-1-TIM3 were significantly increased in EAOC ( < 0.05).
the dysregulation of TILs, TAMs, and T-cell exhaustion might play a role in the malignization of OE to EAOC.
卵巢子宫内膜异位症（OE）和与子宫内膜异位症相关的卵巢癌（EAOC）之间的关联已得到广泛证实，免疫系统功能障碍可能与此相关。本研究的主要目的是确定并比较 OE 和 EAOC 中肿瘤浸润淋巴细胞（TIL）和肿瘤相关巨噬细胞（TAM）的空间分布。次要目标包括分析两组中免疫抑制群体与 T 细胞耗竭标志物之间的关系。
采用免疫化学法检测 TIL（CD3、CD4 和 CD8）和巨噬细胞（CD163）。在石蜡包埋样本上通过免疫荧光法评估耗竭标志物（PD-1、TIM3、CD39 和 FOXP3）及其与肿瘤相关巨噬细胞（CD163）的关系，共纳入 43 例 OE 和 54 例 EAOC 患者。
我们观察到 OE 中主要为上皮内 CD3+分布，而 EAOC 中既有上皮内也有基质分布（<0.001）。OE 中 TIL 更为丰富（<0.001），但 EAOC 中更高的 TIL 与更长的总生存期和无病生存期显著相关（<0.05）。在中度/强度 CD4 EAOC 中，CD39 和 FOXP3 在上皮水平上与 CD163 显著相关（<0.05），而在中度/强度 CD8+、PD-1+和 TIM3+中，PD-1+和 TIM3+显著相关（=0.009）。最后，EAOC 中 T 细胞耗竭标志物 FOXP3-CD39 减少，PD-1-TIM3 显著增加（<0.05）。
TIL、TAM 和 T 细胞耗竭的失调可能在 OE 向 EAOC 恶变中发挥作用。
