PO.TB10.06 · 肿瘤生物学
将组织和腹腔细胞学中的肿瘤浸润免疫细胞与子宫内膜癌的分子标志物相关联
Linking tumor-infiltrating immune cells from tissue and peritoneal cytology to molecular markers in endometrial cancer
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摘要 Abstract
中文摘要
背景
子宫内膜癌中肿瘤浸润淋巴细胞（TILs）的组成可能与临床病理因素及潜在的分子改变均相关。我们旨在表征从新鲜肿瘤组织和腹腔冲洗液细胞学中获取的TIL亚群，并确定这些免疫谱与常规使用的免疫组化标志物之间的关系。
方法
从签署知情同意书的子宫内膜癌患者获取新鲜手术标本和腹腔冲洗液。分离单个核细胞并通过流式细胞术分析，以定量CD3⁻CD19⁺ B细胞、CD3⁻CD16⁺CD56⁺自然杀伤（NK）细胞、CD4⁺CD25⁺调节性T细胞（Tregs）以及CD3⁺CD8⁺细胞毒性T细胞。根据组织病理特征和免疫组化结果对这些细胞群进行比较，包括淋巴血管间隙浸润（LVSI）、PD-L1、雌激素受体（ER）、p53、HER2、错配修复蛋白（MLH1、MSH2、MSH6、PMS2）以及微卫星不稳定性（MSI）状态。
结果
共60份来自子宫内膜癌标本的免疫谱可评估。在LVSI阳性肿瘤中观察到较高比例的CD3⁻CD19⁺ B细胞，而ER阳性肿瘤中该亚群水平较低（两者p<0.05）。CD3⁻CD16⁺CD56⁺ NK细胞在错配修复缺陷（dMMR）病例中更为常见。CD4⁺CD25⁺ Tregs在ER阳性肿瘤中减少（p<0.05）。CD3⁺CD8⁺细胞毒性T细胞在HER2阳性肿瘤中较少见，但在dMMR病例中增加。免疫亚群与所检测的其他免疫组化标志物之间未检出其他显著关联。
结论
从子宫内膜肿瘤组织和腹腔冲洗液细胞学获取的免疫细胞谱似乎能够捕捉关键的临床病理及分子特征，尤其是LVSI、ER、HER2和错配修复状态。需要在整合肿瘤学结局数据的更大队列中进行验证，以明确这些免疫特征的预后及潜在预测相关性。
查看英文原文 English abstract
Background
The composition of tumor-infiltrating lymphocytes (TILs) in endometrial cancer may be linked to both clinicopathologic factors and underlying molecular alterations. We sought to characterize TIL subsets recovered from fresh tumor tissue and peritoneal washing cytology and to determine how these immune profiles relate to routinely used immunohistochemical markers.
Methods
Fresh surgical specimens and peritoneal washings were obtained from patients with endometrial cancer who provided informed consent. Mononuclear cells were isolated and analyzed by flow cytometry to quantify CD3⁻CD19⁺ B cells, CD3⁻CD16⁺CD56⁺ natural killer (NK) cells, CD4⁺CD25⁺ regulatory T cells (Tregs), and CD3⁺CD8⁺ cytotoxic T cells. These populations were compared according to histopathologic features and immunohistochemical results, including lymphovascular space invasion (LVSI), PD-L1, estrogen receptor (ER), p53, HER2, mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), and microsatellite instability (MSI) status.
Results
Sixty immune profiles derived from endometrial cancer specimens were evaluable. Higher proportions of CD3⁻CD19⁺ B cells were observed in LVSI-positive tumors, whereas ER-positive tumors showed lower levels of this subset (both p<0.05). CD3⁻CD16⁺CD56⁺ NK cells were more prevalent in cases with deficient mismatch repair (dMMR). CD4⁺CD25⁺ Tregs were reduced in ER-positive tumors (p<0.05). CD3⁺CD8⁺ cytotoxic T cells were less frequent in HER2-positive tumors but increased in dMMR cases. No additional significant associations were detected between immune subsets and the other immunohistochemical markers examined.
Conclusions
Immune cell profiles obtained from endometrial tumor tissue and peritoneal washing cytology appear to capture key clinicopathologic and molecular features, particularly LVSI, ER, HER2, and mismatch repair status. Validation in larger cohorts with integrated oncologic outcome data is needed to clarify the prognostic and potential predictive relevance of these immune signatures.
利益披露 Disclosure
S. Lee, None..
J. Kim, None..
S. Lee, None..
E. Nam, None..
J. Seo, None..
S. Shin, None.