淋巴细胞激活基因 3 (LAG-3) 是一种免疫检查点受体，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，LAG-3 和程序性细胞死亡受体 1 (PD-1) 的双重抑制可显着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 免疫疗法反应的生物标志物的效用具有重要的临床意义。本研究旨在评估转移性黑色素瘤中基于抗 LAG-3 和抗 PD-1 的免疫治疗后基线 LAG-3 表达与临床结果之间的关联。对治疗前福尔马林固定、石蜡包埋的转移性黑色素瘤标本进行 LAG-3 免疫组织化学（克隆 D2G4O），这些标本来自 53 名接受抗 LAG-3  抗 PD-1 联合疗法治疗的患者。 11 名患者之前接受过基于抗 PD-1 的治疗。根据实体瘤疗效评估标准 (RECIST)，将患者分为有反应者（完全/部分反应；n = 36）或无反应者（疾病稳定/进展；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 和树突状细胞染色。与无反应者相比，有反应者显示出明显更高的 LAG-3 细胞比例 (P = .0210)。 LAG-3表达与TIL评分呈正相关(P < .01)。不同转移部位之间LAG-3表达无显着差异(P > .05)。与 LAG-3 表达≥<1% 的患者相比，肿瘤中 LAG-3 细胞≥1% 的患者的 PFS 显着更长 (P=0.0037)。两组之间的总生存期没有观察到显着差异（P = .1417）。因此，通过 IHC 对 LAG-3 表达的评估值得进一步评估，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。© 2023 作者。经泰勒许可出版

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; n = 36) or non-responders (stable/progressive disease; n = 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 (P = .0210). LAG-3 expression positively correlated with TIL score (P < .01). There were no significant differences in LAG-3 expression between different sites of metastases (P > .05). Patients with ≥ 1% LAG-3+ cells in their tumors had significantly longer PFS compared to patients with < 1% LAG-3 expression (P = .0037). No significant difference was observed in overall survival between the two groups (P = .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.© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.