Lymphocyte-activation gene 3 and T cell immunoreceptor with Ig and ITIM domains (LAG3 and TIGIT)

This target profile describes the synergistic immunosuppressive axis formed by Lymphocyte-activation gene 3 (LAG3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), specifically regarding their role in Regulatory T cell (Treg) mediated suppression of Dendritic Cells (DCs). LAG3 is a co-inhibitory receptor that binds to MHC class II molecules on DCs with higher affinity than CD4, leading to the inhibition of DC maturation and reduced antigen presentation capacity (PubMed: 15034577). TIGIT is a parallel checkpoint receptor that binds to CD155 (PVR) on DCs, signaling through the ITIM domain to induce an immunotolerogenic DC phenotype characterized by increased IL-10 and decreased IL-12 secretion (PubMed: 19011627). In the tumor microenvironment, Tregs highly express both LAG3 and TIGIT, which work in concert to disable DC-mediated activation of effector T cells, facilitating immune evasion (PubMed: 24813887). Therapeutic strategies utilizing monoclonal antibodies like Relatlimab and Tiragolumab aim to block these interactions to reinvigorate the immune system. By disrupting this Treg-DC inhibitory loop, these drugs restore the functional capacity of Dendritic Cells to prime and activate cytotoxic T lymphocytes, often showing enhanced efficacy when combined with PD-1/PD-L1 inhibitors (Source: Bristol Myers Squibb; Roche).

Other names

LAG-3CD223TIGITWUCAMVSTM3VSIG9Lymphocyte-activation gene 3 proteinT-cell immunoreceptor with Ig and ITIM domains

Antagonism of LAG3 and TIGIT receptors to block inhibitory signaling in T cells and Regulatory T cells (Tregs), thereby preventing the suppression of Dendritic Cells and restoring anti-tumor effector T cell activity.