头颈部淋巴上皮样癌中多种抑制性检查点的表达谱及预后价值。
Expression Profiles and Prognostic Value of Multiple Inhibitory Checkpoints in Head and Neck Lymphoepithelioma-Like Carcinoma.
机构信息
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
Department of Medical Oncology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
出版信息
Front Immunol. 2022 Jan 24;13:818411. doi: 10.3389/fimmu.2022.818411. eCollection 2022.
BACKGROUND
Inhibitory checkpoints are promising antitumor targets and predictive biomarkers in a variety of cancers. We aimed to identify the expression levels and prognostic value of multiple inhibitory checkpoints supported by preclinical and clinical evidence in head and neck lymphoepithelioma-like carcinoma (HNLELC).
METHODS
The expression of seven inhibitory checkpoints were evaluated in the tumor nest (TN) and tumor stroma (TS) of 102 HNLELC specimens using immunohistochemistry and digital pathology, and an inhibitory checkpoint-based signature (ICS) was subsequently constructed using the LASSO Cox regression model.
RESULTS
PD-L1, B7H3, and IDO-1 were mostly expressed in the TN, with median H-score of TN vs TS: 63.6 vs 14.6; 8.1 vs 1.0; 61.5 vs 34.7 (all < 0.001), whereas PD-1, TIM-3, LAG-3, and VISTA were mainly observed in the TS, with median H-score of TN vs TS: 0.2 vs 12.4, 3.4 vs 7.1, 6.2 vs 11.9, 16.4 vs 47.2 (all < 0.001), respectively. The most common simultaneously expressed combinations consisted of PD-L1 + B7H3 + IDO-1 + TIM-3 + LAG-3 + VISTA and B7H3 + IDO-1 + TIM-3 + LAG-3 in the TN (both occurring in 8.8% of patients) and PD-L1 + B7H3 + IDO-1 in the TS (4.9%). In addition, high-ICS patients had shorter 5-year disease-free (40.6% vs 81.7%; < 0.001), regional recurrence-free (63.5% vs 88.2%; = 0.003), and overall survival (73.5% vs 92.9%; = 0.006) than low-ICS patients. Multivariate analysis revealed that ICS represented an independent predictor, which could significantly complement the predictive performance of TNM stage for 3-year (AUC 0.724 vs 0.619, = 0.014), 5-year (AUC 0.727 vs 0.640, = 0.056), and 10-year disease-free survival (AUC 0.815 vs 0.709, = 0.023).
CONCLUSIONS
The expression of inhibitory checkpoints and ICS classifier may increase the prognostic value of the TNM staging system and guide the rational design of personalized inhibitory checkpoint blockade therapy in HNLELC.
背景
抑制性检查点是多种癌症中具有前景的抗肿瘤靶点和预测性生物标志物。我们旨在鉴定头颈淋巴上皮样癌（HNLELC）中基于临床前和临床证据支持的多种抑制性检查点的表达水平和预后价值。
方法
使用免疫组织化学和数字病理学方法评估 102 例 HNLELC 标本中肿瘤巢（TN）和肿瘤基质（TS）中七种抑制性检查点的表达，并使用 LASSO Cox 回归模型构建抑制性检查点为基础的特征（ICS）。
结果
PD-L1、B7H3 和 IDO-1 主要在 TN 中表达，TN 与 TS 的中位 H 评分分别为 63.6 比 14.6；8.1 比 1.0；61.5 比 34.7（均 < 0.001），而 PD-1、TIM-3、LAG-3 和 VISTA 主要在 TS 中表达，TN 与 TS 的中位 H 评分分别为 0.2 比 12.4；3.4 比 7.1；6.2 比 11.9；16.4 比 47.2（均 < 0.001）。最常见的同时表达组合包括 PD-L1+B7H3+IDO-1+TIM-3+LAG-3+VISTA 和 B7H3+IDO-1+TIM-3+LAG-3 在 TN 中（均发生在 8.8%的患者中）和 PD-L1+B7H3+IDO-1 在 TS 中（4.9%）。此外，高 ICS 患者的 5 年无病（40.6%比 81.7%； < 0.001）、区域无复发生存（63.5%比 88.2%； = 0.003）和总生存（73.5%比 92.9%； = 0.006）均低于低 ICS 患者。多变量分析显示，ICS 是一个独立的预测因子，它可以显著补充 TNM 分期对 3 年（AUC 0.724 比 0.619， = 0.014）、5 年（AUC 0.727 比 0.640， = 0.056）和 10 年无病生存（AUC 0.815 比 0.709， = 0.023）的预测性能。
结论
抑制性检查点的表达和 ICS 分类器可能增加 TNM 分期系统的预后价值，并指导 HNLELC 中抑制性检查点阻断治疗的个体化合理设计。
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