Online first
Review paper
Published online: 2025-01-15
T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) — an update on emerging negative immune checkpoints in cancer treatment
1
Abstract
Immunotherapy is currently one of the most important treatment options for patients with various cancers. It is predominantly based on immune checkpoint inhibitors (ICIs), which are supposed to reverse immune suppression caused by interactions of negative immune checkpoints with their ligands. Cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand, programmed death ligand 1 (PD-L1) are the checkpoints targeted by antibodies registered in various types of cancer to enable effective anti-cancer immune response. Despite numerous possibilities, other molecules belonging to immune checkpoints — T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), are being extensively researched, mainly due to their role in cancer progression and resistance to immunotherapy. Recently, the first antibody against LAG-3 — relatlimab has been registered in melanoma, and many others are tested in the final stages of clinical trials. Thus, understanding their intricate functions and developing strategies to use them can create opportunities to apply immunotherapy in cancer treatment. This article describes their characteristics and potential role in solid-tumor treatment with TIM-3, LAG-3, and TIGIT molecules, which have been connected to tumor progression, poor survival, and poor prognosis in many tumor types.
Keywords: TIM-3LAG-3TIGITimmunotherapynegative immune checkpointssolid tumors
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