Abi-Aad Sasha-Jane, Zouein Joseph, Chartouni Antoine, Naim Nabih, Kourie Hampig Raphael
Hematology-Oncology Department, Faculty of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon.
Immunotherapy. 2023 Jun;15(8):611-618. doi: 10.2217/imt-2022-0185. Epub 2023 Apr 3.
Immunotherapy has improved the prognosis of many cancers, yet a large number of patients have demonstrated resistance to current immune checkpoint inhibitors. LAG-3 is an immune checkpoint expressed on tumor-infiltrating lymphocytes CD4 and CD8, Tregs and other immune cells. Coexpression of PD-1 and LAG-3 in solid or hematological cancers is generally associated with a poor prognosis and may be responsible for immunotherapy resistance. Dual inhibition therapy in the RELATIVITY-047 trial significantly improved progression-free survival in metastatic melanoma. This article discusses the presence of a possible synergistic interaction between LAG-3 and PD-1 in the tumor microenvironment and the utility of targeting both immune checkpoint inhibitors as an effective way to bypass resistance and increase treatment efficacy.
免疫疗法改善了许多癌症的预后，但仍有大量患者对目前的免疫检查点抑制剂表现出耐药性。淋巴细胞活化基因-3（LAG-3）是一种在肿瘤浸润淋巴细胞CD4和CD8、调节性T细胞（Tregs）及其他免疫细胞上表达的免疫检查点。实体癌或血液系统癌症中PD-1和LAG-3的共表达通常与预后不良相关，可能是免疫疗法耐药的原因。在“相对论-047”试验中的双重抑制疗法显著改善了转移性黑色素瘤的无进展生存期。本文讨论了肿瘤微环境中LAG-3与PD-1之间可能存在的协同相互作用，以及靶向两种免疫检查点抑制剂作为绕过耐药性并提高治疗效果的有效方法的实用性。
