LAG3 IHC Melanoma

Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor protein expressed on the cell surface of multiple immune cell types including effector T cells, regulatory T cells (Tregs), NK cells, B cells, and plasmacytoid dendritic cells. When engaged, LAG3 functions by delivering inhibitory signals that regulate immune cell homeostasis, T cell activation, proliferation, cytokine production, and cytolytic activity. Preclinical studies suggest that inhibiting LAG3 allows T cells to regain their cytotoxic function and potentially affect tumor growth. LAG3 expression is also being evaluated as a biomarker to predict response to treatment. Early research suggests that targeting the LAG3 pathway in combination with other potentially complementary immune pathways may be a key strategy to more effectively activate the antitumor immune response. In advanced melanoma, inhibition of LAG3 and PD-L1 provided improved progression-free survival than inhibition of PD-1 alone. While a >1% cutoff for LAG3 positivity is used for this test, there was also a benefit of the combination therapy in patients with <1% LAG3.