淋巴细胞活化基因-3在妇科肿瘤中的研究进展

doi:10.12280/gjfckx.20240456

摘要/Abstract

摘要：

妇科肿瘤是女性死亡的重要原因之一，尽管经过规范治疗部分患者的病情可以得到改善，但仍有很大一部分患者病情恶化，预后不佳。早期诊断及治疗是改善妇科肿瘤预后、减轻疾病负担的重要方法，因此需寻找更有效的治疗靶点。淋巴细胞活化基因-3（lymphocyte activation gene-3，LAG-3）是一个新兴的免疫检查点分子，高表达于多种类型的肿瘤浸润淋巴细胞表面，通过抑制免疫细胞功能参与免疫抑制并造成肿瘤免疫逃逸。近年研究发现，LAG-3在妇科肿瘤中高表达，与肿瘤的发生发展密切相关，有望成为妇科肿瘤免疫治疗的新靶点。阐述LAG-3的结构及功能，并就LAG-3与三大妇科肿瘤的相关性研究进展进行综述，以期为妇科肿瘤的后续治疗研究提供新的思路。

关键词: 生殖器肿瘤, 女（雌）性, 免疫检查点抑制剂, 抗肿瘤药, 肿瘤微环境, 免疫疗法, 淋巴细胞活化基因-3

Abstract:

Gynecological tumors are one of the important causes of death among women. Although standard treatments can improve the condition of some patients, many still experience disease progression and poor prognosis. Early diagnosis and treatment are crucial for improving the prognosis of gynecological tumors and reducing the burden of disease. Therefore, identifying more effective therapeutic targets is essential. Lymphocyte activation gene-3 (LAG-3) is an emerging immune checkpoint molecule that is highly expressed on the surface of tumor infiltrating lymphocytes in various types of tumors. It participates in immune suppression and tumor immune evasion by inhibiting the function of immune cells. Recent studies have shown that LAG-3 is highly expressed in gynecological tumors and is closely associated with tumor development, making it a promising new target for immunotherapy in gynecological tumors. This review outlines the structure and function of LAG-3 and discusses the research progress on its association with the three major gynecological tumors, providing new insights for future therapeutic research in gynecological tumors.

Key words: Genital neoplasms, female, Immune checkpoint inhibitors, Antineoplastic agents, Tumor microenvironment, Immunotherapy, Lymphocyte activation gene-3

白耀俊, 胡晓红, 李红丽, 刘畅. 淋巴细胞活化基因-3在妇科肿瘤中的研究进展[J]. 国际妇产科学杂志, 2024, 51(5): 566-571.

BAI Yao-jun, HU Xiao-hong, LI Hong-li, LIU Chang. Research Progress on Lymphocyte Activation Gene-3 in Gynecological Tumors[J]. Journal of International Obstetrics and Gynecology, 2024, 51(5): 566-571.

图/表 2

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药物名称	药物类型	组合剂	阶段	临床试验编号	状态	研究结果
Relatlimab（BMS986016）	抗LAG-3	Ipilimumab, Cyclophosphamid, Fludarabine Phosphate, Tumor Infiltrating Lymphocytes infusion, Nivolumab	Ⅰ，Ⅱ	NCT04611126	完成（2024-07-02）	尚未提交
Tebotelimab（MGD013）	抗PD-1和抗LAG-3	Margetuximab（抗HER2）	Ⅰ	NCT03219268	完成（2023-02-08）	尚未提交
INCAGN02385	抗LAG-3	-	Ⅰ	NCT03538028	完成（2020-10-07）	尚未提交
Relatlimab（BMS986016）	抗LAG-3	Adavosertib, Afatinib, Dimaleate, Nivolumab, Osimertinib, Palbociclib, Pertuzumab, PI3K-beta, FGFR Inhibitor AZD4547	Ⅱ	NCT02465060	进行（估计2025-12）	尚未提交
XmAb22841	抗CTLA-4和抗LAG-3	Pembrolizumab（抗PD-1）	Ⅰ	NCT03849469	完成（2023-02-16）	尚未提交
LAG-525	抗LAG-3	PDR001型（抗PD-1）	Ⅱ	NCT03365791	完成（2020-09-17）	已公布
BMS986016	抗LAG-3	抗PD-1	Ⅰ	NCT01968109	招募	尚未提交

药物名称	药物类型	组合剂	阶段	临床试验编号	状态	研究结果
Relatlimab（BMS986016）	抗LAG-3	Ipilimumab, Cyclophosphamid, Fludarabine Phosphate, Tumor Infiltrating Lymphocytes infusion, Nivolumab	Ⅰ，Ⅱ	NCT04611126	完成（2024-07-02）	尚未提交
Tebotelimab（MGD013）	抗PD-1和抗LAG-3	Margetuximab（抗HER2）	Ⅰ	NCT03219268	完成（2023-02-08）	尚未提交
INCAGN02385	抗LAG-3	-	Ⅰ	NCT03538028	完成（2020-10-07）	尚未提交
Relatlimab（BMS986016）	抗LAG-3	Adavosertib, Afatinib, Dimaleate, Nivolumab, Osimertinib, Palbociclib, Pertuzumab, PI3K-beta, FGFR Inhibitor AZD4547	Ⅱ	NCT02465060	进行（估计2025-12）	尚未提交
XmAb22841	抗CTLA-4和抗LAG-3	Pembrolizumab（抗PD-1）	Ⅰ	NCT03849469	完成（2023-02-16）	尚未提交
LAG-525	抗LAG-3	PDR001型（抗PD-1）	Ⅱ	NCT03365791	完成（2020-09-17）	已公布
BMS986016	抗LAG-3	抗PD-1	Ⅰ	NCT01968109	招募	尚未提交

药物名称	药物类型	联合	阶段	临床试验编号	状态	研究结果
Tebotelimab（MGD013）	抗PD-1和抗LAG-3	Margetuximab（抗HER2）	Ⅰ	NCT03219268	完成（2023-02-08）	尚未提交
XmAb22841	抗CTLA-4和抗LAG-3	Pembrolizumab（抗PD-1）	Ⅰ	NCT03849469	完成（2023-02-16）	尚未提交
Relatlimab	抗LAG-3	抗PD-1	Ⅰ，Ⅱ	NCT02488759	招募	-
INCAGN02385	抗LAG-3	-	Ⅰ	NCT03538028	完成（2020-10-07）	尚未提交
INCAGN02385	抗LAG-3	抗PD-1	Ⅰ，Ⅱ	NCT01968109	招募	-

药物名称	药物类型	联合	阶段	临床试验编号	状态	研究结果
Tebotelimab（MGD013）	抗PD-1和抗LAG-3	Margetuximab（抗HER2）	Ⅰ	NCT03219268	完成（2023-02-08）	尚未提交
XmAb22841	抗CTLA-4和抗LAG-3	Pembrolizumab（抗PD-1）	Ⅰ	NCT03849469	完成（2023-02-16）	尚未提交
Relatlimab	抗LAG-3	抗PD-1	Ⅰ，Ⅱ	NCT02488759	招募	-
INCAGN02385	抗LAG-3	-	Ⅰ	NCT03538028	完成（2020-10-07）	尚未提交
INCAGN02385	抗LAG-3	抗PD-1	Ⅰ，Ⅱ	NCT01968109	招募	-