Simultaneous inhibition of PD-1 and LAG-3: the future of immunotherapy?

被引:13
作者
Abi-Aad, Sasha-Jane [1 ]
Zouein, Joseph [1 ]
Chartouni, Antoine [1 ]
Naim, Nabih [1 ]
Kourie, Hampig Raphael [1 ]
机构
[1] St Joseph Univ Beirut, Fac Med, Oncol Dept, Hematology, Beirut, Lebanon
关键词
anti-LAG-3; immune checkpoint inhibitors; LAG-3; relatlimab; ACQUIRED-RESISTANCE; CANCER; RELATLIMAB; NIVOLUMAB; TIM-3;
D O I
10.2217/imt-2022-0185
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. Tweetable abstractCoexpression of PD-1 and LAG-3 in solid or hematological cancers may be responsible for immunotherapy resistance; therefore, dual inhibition of PD-1 and LAG-3 may improve treatment efficacy. Plain language summaryImmunotherapy has increased survival rates for many cancer types; however, a large number of individuals experience resistance to this therapy and poor outcomes. Among the immune molecules expressed on immune cells and tumor cells, LAG-3 can favor tumor escape and progression. The coexpression of multiple immune molecules such as PD-1 and LAG-3 in multiple cancers is generally associated with a worse prognosis and might be contributing to immunotherapy failure. Dual inhibition therapy, targeting both PD-1 and LAG-3, in the RELATIVITY-047 study has shown great antitumor activity and improved survival in metastatic melanoma. This report discusses a possible synergistic interaction between LAG-3 and PD-1 within the tumor and the utility of targeting both molecules as a way to overcome resistance and improve treatment efficacy.
引用
收藏
页码:611 / 618
页数:8
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