新型检查点靶基因淋巴细胞激活基因 3 在皮肤鳞状细胞癌中高表达。

The Novel Checkpoint Target Lymphocyte-Activation Gene 3 Is Highly Expressed in Cutaneous Squamous Cell Carcinoma.

机构信息

The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York.

Department of Dermatology, Virginia Commonwealth University, Richmond, Virginia.

出版信息

Dermatol Surg. 2023 Dec 1;49(12):1112-1115. doi: 10.1097/DSS.0000000000004006. Epub 2023 Nov 7.

DOI:10.1097/DSS.0000000000004006

PMID:37962130

Abstract

BACKGROUND

Lymphocyte activation-gene 3 (LAG-3) is an emerging next-generation immune checkpoint molecule. We aim to define the expression pattern of LAG-3 in cutaneous squamous cell carcinoma (cSCC) as a first step to understand the role of LAG-3 in cSCC prognosis and therapy.

OBJECTIVE

To define the expression pattern of LAG-3 in cSCC as a first step to understand the role of LAG-3 in cSCC prognosis and therapy.

METHODS

To test whether LAG-3 is expressed on cSCC infiltrating lymphocytes, we isolated CD8 + T lymphocytes from three SCC tumors using flow cytometry and performed single-cell RNA sequencing for LAG-3 and programmed cell death protein -1 (PD-1). In addition, we evaluated LAG-3 mRNA expression in formalin-fixed, paraffin-embedded tissue using NanoString technology.

RESULTS

Single-cell RNA sequencing showed that LAG-3 is expressed more than PD-1 in CD8 + tumor infiltrating lymphocytes (50.8% vs 35.2%, respectively). Quantifying LAG-3 mRNA expression showed that compared with normal skin, LAG-3 mRNA is approximately 8 fold higher in immunocompetent associated SCC tumors and approximately 2 fold higher in transplant associated SCC tumors ( p -values <.05). In addition, LAG-3 mRNA was expressed 7.2 fold higher in T2a SCC tumors compared with normal skin ( p -value <.05).

CONCLUSION

Lymphocyte activation-gene 3 is expressed on SCC infiltrating T lymphocytes at a higher percentage than PD-1. In addition, LAG-3 mRNA expression is significantly higher in SCC tumors. Ongoing studies will be performed to define its role as an immune-related biomarker and as a therapeutic target.

摘要

背景

淋巴细胞激活基因 3（LAG-3）是一种新兴的下一代免疫检查点分子。我们旨在确定 LAG-3 在皮肤鳞状细胞癌（cSCC）中的表达模式，作为了解 LAG-3 在 cSCC 预后和治疗中的作用的第一步。

目的

确定 LAG-3 在 cSCC 中的表达模式，作为了解 LAG-3 在 cSCC 预后和治疗中的作用的第一步。

方法

为了测试 LAG-3 是否在 cSCC 浸润淋巴细胞上表达，我们使用流式细胞术从三个 SCC 肿瘤中分离 CD8+T 淋巴细胞，并对 LAG-3 和程序性细胞死亡蛋白-1（PD-1）进行单细胞 RNA 测序。此外，我们使用 NanoString 技术评估了福尔马林固定、石蜡包埋组织中的 LAG-3 mRNA 表达。

结果

单细胞 RNA 测序显示，LAG-3 在 CD8+肿瘤浸润淋巴细胞中的表达高于 PD-1（分别为 50.8%和 35.2%）。定量 LAG-3 mRNA 表达显示，与正常皮肤相比，免疫相关 SCC 肿瘤中的 LAG-3 mRNA 约高 8 倍，移植相关 SCC 肿瘤中的 LAG-3 mRNA 约高 2 倍（p 值<.05）。此外，与正常皮肤相比，T2a SCC 肿瘤中的 LAG-3 mRNA 表达高 7.2 倍（p 值<.05）。