Expression Profiles and Prognostic Value of Multiple Inhibitory Checkpoints in Head and Neck Lymphoepithelioma-Like Carcinoma

Frontiers in Immunology

Immunology

Wei-Jie Luo¹  Yan-Fen Feng²  Fang Liu³  Xue-Liang Fang⁴  Ye-Lin Liang⁴  Ya-Qin Wang⁴  Yan-Ping Mao⁴  Wen-Qing Zou⁴  Na Liu⁴  Shao-Bo Liang⁵ 

[1] Department of Medical Oncology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China;Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China;Department of Pathology, The First People’s Hospital of Foshan, Foshan, China;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 Radiation Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;

关键词: head and neck lymphoepithelioma-like carcinoma;    multiple inhibitory checkpoints;    tumor microenvironment;    TNM stage;    prognosis;   

DOI  :  10.3389/fimmu.2022.818411

 received in 2021-11-19, accepted in 2022-01-04,  发布年份 2022

来源: Frontiers

【 摘 要 】

BackgroundInhibitory 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).MethodsThe 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.ResultsPD-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 P < 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 P < 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%; P < 0.001), regional recurrence-free (63.5% vs 88.2%; P = 0.003), and overall survival (73.5% vs 92.9%; P = 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, P = 0.014), 5-year (AUC 0.727 vs 0.640, P = 0.056), and 10-year disease-free survival (AUC 0.815 vs 0.709, P = 0.023).ConclusionsThe 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.

【 授权许可】

Unknown   
Copyright © 2022 Zou, Luo, Feng, Liu, Liang, Fang, Liang, Liu, Wang and Mao