肿瘤细胞治疗研究
英文原题：Prognostic impact of HLA-G expression in cervical squamous cell carcinoma: correlation with PD-L1 and CD8-positive tumor infiltrating lymphocytes.
Prognostic impact of HLA-G expression in cervical squamous cell carcinoma: correlation with PD-L1 and CD8-positive tumor infiltrating lymphocytes.
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本研究证实，HLA-G/sHLA-G表达升高是宫颈癌的独立不良预后因素。
本研究的目的是探讨 HLA-G 表达在宫颈鳞状细胞癌（CSCC）患者中的预后影响，并进一步分析其与肿瘤微环境（TME）中 PD-L1 及 CD8 阳性（CD8+）TIL（肿瘤浸润淋巴细胞）的相关性。
共收集 139 例诊断为 CSCC 患者的福尔马林固定石蜡包埋（FFPE）组织样本。采用免疫组织化学（IHC）和多重免疫荧光（mIF）染色评估免疫生物标志物的表达，包括 HLA-G、其受体 ILT2、PD-L1、总 TIL 和 CD8+ TIL。
HLA-G 的总体阳性表达率为 86.8%，sHLA-G 为 85.1%，PD-L1 为 50.0%，TME 中 TIL 低浸润病例为 70.2%。
Purpose of the study was to investigate the prognostic impact of HLA-G expression in patients with cervical squamous cell carcinoma (CSCC), and to further analyze its correlations with PD-L1 and CD8-positive (CD8 + ) tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME).
A total of 139 formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from patients diagnosed with CSCC. Immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) staining were performed to assess the expression of immune biomarkers, including HLA-G, its receptor ILT2, PD-L1, total TILs and CD8 + TILs.
The overall positive expression rates were 86.8% for HLA-G, 85.1% for sHLA-G, 50.0% for PD-L1, and 70.2% for cases with low TIL infiltration in the TME. These immune biomarkers displayed distinct immunoreactivity patterns with remarkable intratumoral and stromal heterogeneity. ILT2 expression was positively correlated with CD8 + TIL infiltration in both intratumoral and stromal compartments, yet rare cellular co-localization between ILT2 and CD8 was detected. Within tumoral regions, a strong positive correlation was identified between HLA-G and PD-L1 expression, and the two proteins were confirmed to be co-localized at the single-cell level in SCC lesions. Using the median HLA-G expression level of 61.0% as the cutoff value, patients with HLA-G expression above this threshold showed significantly worse overall survival (OS). The subgroup with high HLA-G/sHLA-G and low TIL infiltration showed the worst prognosis.
The present study confirms that elevated HLA-G/sHLA-G expression serves as an independent adverse prognostic factor for cervical cancer. Combined assessment of HLA-G, PD-L1 and TIL infiltration may enable risk-stratified prognostic management for patients with cervical cancer.
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