1. Lymphocyte activating gene 3 protein expression in nasopharyngeal carcinoma is correlated with programmed cell death-1 and programmed cell death ligand-1, tumor-infiltrating lymphocytes
- Author
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Li Zhang, Feiteng Lu, Yan Huang, Hongyun Zhao, Kangmei Zeng, Jia-Xin Cao, Wen-Juan Ma, and Fan Luo
- Subjects
PD-L1 ,Cancer Research ,medicine.medical_treatment ,Lymphocyte ,GZMB ,LAG-3 ,PD-1 ,Genetics ,Medicine ,RC254-282 ,Survival analysis ,QH573-671 ,biology ,Tumor-infiltrating lymphocytes ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,Immunotherapy ,medicine.disease ,CD3 ,medicine.anatomical_structure ,Oncology ,Nasopharyngeal carcinoma ,biology.protein ,Cancer research ,Cytology ,business ,Primary Research ,NPC - Abstract
Background Immunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, however, its relationship with NPC remains unclear. This study aimed to evaluate LAG-3 expression in NPC and its association with CD3+ tumor-infiltrating lymphocytes (TILs), Granzyme B (GZMB), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) expression. Methods A total of 182 patients with NPC from Sun Yat-sen University Cancer Center, China, were included in this retrospective study. LAG-3 expression in 15 NPC cell lines and LAG-3, CD3+ TILs, GZMB, PD-L1 and PD-1 in clinical samples were estimated using immunohistochemistry. The Chi-square test was used to estimate the association between LAG-3, other biomarkers, and clinical characteristics. Survival analysis was performed using the Kaplan–Meier method and the Cox regression model. Results LAG-3 was negatively expressed in all of the 15 NPC cell lines, whereas, 147 patients with NPC (80.8%) exhibited high LAG-3 expression on TILs from tumor tissues. Male patients and those who were EBV-positive presented higher LAG-3 expression. Correlation analyses showed that LAG-3 expression was related to PD-1 expression on TILs, as well as, PD-L1 expression on tumor cells (TCs) and TILs. Both the univariate and multivariate Cox models indicated that pathological type III (P = 0.036), higher LAG-3 on TILs (P P = 0.027), and higher PD-1 on TILs (P P = 0.002). Conclusion Higher LAG-3 and PD-1 on TILs, and higher PD-L1 expression on TCs, and pathological type III were identified as independent risk factors for poorer DFS in NPC patients. Our data demonstrate that LAG-3 is a promising inhibitory receptor that may play an important role in anti-NPC therapy.
- Published
- 2021