免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
接受抗 Lag-3 + 抗 PD-1 联合免疫治疗的转移性黑色素瘤患者的 Lag-3 表达与临床结局
英文原题：Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies.
查看英文原题
Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies.
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中文摘要
淋巴细胞活化基因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免疫逃逸。与单独抗PD-1治疗相比，联合抑制LAG-3和程序性细胞死亡受体1（PD-1）显著改善了转移性黑色素瘤患者的无进展生存期（PFS）。
因此，评估LAG-3表达能否作为抗LAG-3联合抗PD-1免疫治疗的应答生物标志物，具有重要临床意义。本研究评估转移性黑色素瘤患者治疗前LAG-3表达与接受抗LAG-3和抗PD-1为基础的免疫治疗后临床结局的关联。对53例患者治疗前转移性黑色素瘤标本进行LAG-3免疫组化（克隆号D2G4O）；其中11例既往接受过抗PD-1为基础的治疗。依据实体瘤疗效评价标准（RECIST），将患者分为应答者（完全/部分缓解，n=36）和无应答者（疾病稳定/进展，n=17）。在苏木精-伊红染色切片上评估TIL（肿瘤浸润淋巴细胞）。81%的患者可检测到LAG-3表达，主要见于TIL和树突状细胞。应答者LAG-3阳性细胞比例显著高于无应答者（P=0.0210）。LAG-3表达与TIL评分呈正相关（P<0.01）。不同转移部位间LAG-3表达无显著差异（P>0.05）。肿瘤内LAG-3阳性细胞≥1%的患者PFS显著长于表达<1%的患者（P=0.0037），但两组总生存期无显著差异（P=0.1417）。
因此，仍需进一步评估免疫组化检测LAG-3表达作为转移性黑色素瘤应答和生存预测标志物的价值。
展开英文摘要原文
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.
论文信息
- 作者
- Gide TN、Paver EC、Yaseen Z、Maher N、Adegoke N、Menzies AM、Pires da Silva I、Wilmott JS
- 单位
- Melanoma Institute Australia, The University of Sydney, Sydney, Australia.Australia
- 文献类型
- 非美国政府资助研究
- 期刊
- Oncoimmunology2023
- 原文标识
- PubMed 37808404 · DOI 10.1080/2162402X.2023.2261248
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