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.
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