Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
Charles Perkins Centre, The University of Sydney, Sydney, Australia.
Oncoimmunology. 2023 Oct 4;12(1):2261248. doi: 10.1080/2162402X.2023.2261248. eCollection 2023.
Lymphocyte-activation gene-3 (LAG-3), an immune checkpoint receptor, negatively regulates T-cell function and facilitates immune escape of tumors. Dual inhibition of LAG-3 and programmed cell death receptor-1 (PD-1) significantly improved progression-free survival (PFS) in metastatic melanoma patients compared to anti-PD-1 therapy alone. Investigating the utility of LAG-3 expression as a biomarker of response to anti-LAG-3 + anti-PD-1 immunotherapy is of great clinical relevance. This study sought to evaluate the association between baseline LAG-3 expression and clinical outcomes following anti-LAG-3 and anti-PD-1-based immunotherapy in metastatic melanoma. LAG-3 immunohistochemistry (clone D2G4O) was performed on pre-treatment formalin-fixed, paraffin-embedded metastatic melanoma specimens from 53 patients treated with combination anti-LAG-3 + anti-PD-1-based therapies. Eleven patients had received prior anti-PD-1-based treatment. Patients were categorized as responders (complete/partial response; = 36) or non-responders (stable/progressive disease; = 17) based on the Response Evaluation Criteria in Solid Tumours (RECIST). Tumor-infiltrating lymphocytes (TILs) were scored on hematoxylin and eosin-stained sections. LAG-3 expression was observed in 81% of patients, with staining in TILs and dendritic cells. Responders displayed significantly higher proportions of LAG-3+ cells compared to non-responders ( = .0210). LAG-3 expression positively correlated with TIL score ( < .01). There were no significant differences in LAG-3 expression between different sites of metastases ( > .05). Patients with ≥ 1% LAG-3+ cells in their tumors had significantly longer PFS compared to patients with < 1% LAG-3 expression ( = .0037). No significant difference was observed in overall survival between the two groups ( = .1417). Therefore, the assessment of LAG-3 expression via IHC warrants further evaluation to determine its role as a predictive marker of response and survival in metastatic melanoma.
淋巴细胞激活基因 3（LAG-3）是一种免疫检查点受体，可负向调节 T 细胞功能，并促进肿瘤的免疫逃逸。与单独的抗 PD-1 治疗相比，双重抑制 LAG-3 和程序性细胞死亡受体 1（PD-1）可显著改善转移性黑色素瘤患者的无进展生存期（PFS）。研究 LAG-3 表达作为抗 LAG-3+抗 PD-1 免疫治疗反应的生物标志物的效用具有重要的临床意义。本研究旨在评估基线 LAG-3 表达与转移性黑色素瘤患者接受抗 LAG-3 和抗 PD-1 为基础的免疫治疗后的临床结局之间的关系。对 53 例接受抗 LAG-3+抗 PD-1 为基础的联合治疗的转移性黑色素瘤患者的预处理福尔马林固定、石蜡包埋的转移性黑色素瘤标本进行 LAG-3 免疫组化（克隆 D2G4O）。11 例患者曾接受过抗 PD-1 为基础的治疗。根据实体瘤反应评价标准（RECIST），患者被分为应答者（完全/部分缓解；n=36）或无应答者（稳定/进展性疾病；n=17）。在苏木精和伊红染色的切片上对肿瘤浸润淋巴细胞（TIL）进行评分。81%的患者观察到 LAG-3 表达，TIL 和树突状细胞有染色。与无应答者相比，应答者的 LAG-3+细胞比例显著更高（=0.0210）。LAG-3 表达与 TIL 评分呈正相关（<0.01）。不同转移部位的 LAG-3 表达无显著差异（>0.05）。肿瘤中 LAG-3+细胞≥1%的患者与 LAG-3 表达<1%的患者相比，PFS 显著延长（=0.0037）。两组之间的总生存期无显著差异（=0.1417）。因此，通过 IHC 评估 LAG-3 表达值得进一步评估，以确定其作为转移性黑色素瘤反应和生存的预测标志物的作用。
Zotero 插件
