Abstract
BackgroundImmunotherapy 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.MethodsA 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.ResultsLAG-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 < 0.001), higher PD-L1 on TCs (P = 0.027), and higher PD-1 on TILs (P < 0.001) were associated with poorer disease-free survival (DFS). However, lower PD-L1 expression on TILs was related to superior DFS only in the univariate Cox analyses (P = 0.002).ConclusionHigher 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.
Highlights
Immunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC)
Patient clinical characteristics In this study, 297 patients originally diagnosed with NPC at Sun Yat-sen University Cancer Center (SYSUCC) were screened for eligibility, 115 patients did not meet the inclusion criteria, of which 50 patients had no tumor staging or pathological type, four patients had other primary tumors, and 16 patients were lost to follow-up, and 45 patients had insufficient paraffin sections
Lymphocyte activating 3 gene (LAG-3): lymphocyte activating 3; PD-L1: programmed death ligand 1; PD-1: programmed death 1; tumor-infiltrating lymphocytes (TILs): tumor-infiltrating lymphocyte; tumor cells (TCs): tumor cell; Granzyme B (GZMB): granzyme B; NSCLC: non-small cell lung cancer (Low vs. High, HR, 95% confidence intervals (CI) 1.00 vs 0.678 (0.452– 1.017), P = 0.002)
Summary
Immunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, 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. With recent developments in radiotherapy and combined chemoradiotherapy, the survival of NPC patients has been substantially prolonged [3, 4]. Local relapse and distant metastasis continue to represent major causes of cancer progression following anti-NPC therapy [5]. Due to limited advances made regarding chemotherapy regimens, it is critical to explore novel approaches for the treatment of metastatic NPC that alleviate toxicity and promote survival benefits
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