Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies.

IF 7.2 2区 医学
Oncoimmunology Pub Date : 2023-10-04 eCollection Date: 2023-01-01 DOI:10.1080/2162402X.2023.2261248
Tuba N Gide, Elizabeth C Paver, Zarwa Yaseen, Nigel Maher, Nurudeen Adegoke, Alexander M Menzies, Ines Pires da Silva, James S Wilmott, Georgina V Long, Richard A Scolyer
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引用次数: 0

Abstract

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.

Abstract Image

Abstract Image

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Lag-3在接受抗Lag-3+抗PD-1联合免疫疗法治疗的转移性黑色素瘤患者中的表达和临床结果。
淋巴细胞活化基因-3(LAG-3)是一种免疫检查点受体,负调节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)的双重抑制显著提高了转移性黑色素瘤患者的无进展生存率(PFS)。研究LAG-3表达作为抗LAG-3反应的生物标志物的效用 + 抗PD-1免疫疗法具有重要的临床意义。本研究旨在评估转移性黑色素瘤中抗LAG-3和基于抗PD-1的免疫疗法后基线LAG-3表达与临床结果之间的关系。LAG-3免疫组织化学(克隆D2G4O)对53名接受联合抗LAG-3治疗的患者的福尔马林固定、石蜡包埋的转移性黑色素瘤标本进行了预处理 + 基于抗PD-1的疗法。11名患者曾接受过基于抗PD-1的治疗。患者被归类为应答者(完全/部分应答;n = 36)或无应答者(稳定/进行性疾病;n = 17) 基于实体瘤反应评估标准(RECIST)。在苏木精和伊红染色切片上对肿瘤浸润性淋巴细胞(TIL)进行评分。在81%的患者中观察到LAG-3表达,TIL和树突状细胞染色。应答者的LAG-3+细胞比例明显高于无应答者(P = .0210)。LAG-3表达与TIL评分呈正相关(P P > .05)。患有 ≥ 与患有 P = .0037)。两组患者的总生存率差异无统计学意义(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存活的预测标志物的作用。
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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGY-IMMUNOLOGY
CiteScore
12.80
自引率
2.80%
发文量
276
期刊介绍: Tumor immunology explores the natural and therapy-induced recognition of cancers, along with the complex interplay between oncogenesis, inflammation, and immunosurveillance. In response to recent advancements, a new journal, OncoImmunology, is being launched to specifically address tumor immunology. The field has seen significant progress with the clinical demonstration and FDA approval of anticancer immunotherapies. There's also growing evidence suggesting that many current chemotherapeutic agents rely on immune effectors for their efficacy. While oncologists have historically utilized chemotherapeutic and radiotherapeutic regimens successfully, they may have unwittingly leveraged the immune system's ability to recognize tumor-specific antigens and control cancer growth. Consequently, immunological biomarkers are increasingly crucial for cancer prognosis and predicting chemotherapy efficacy. There's strong support for combining conventional anticancer therapies with immunotherapies. OncoImmunology will welcome high-profile submissions spanning fundamental, translational, and clinical aspects of tumor immunology, including solid and hematological cancers, inflammation, and both innate and acquired immune responses.
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