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. 2024 Aug 26;14:1402837. doi: 10.3389/fonc.2024.1402837

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Copyright © 2024 Luo, Cai, Yang, Lu, Yi and Wu

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The immunosuppression mechanisms of LAG-3 in the tumor microenvironment. (1) The interaction between LAG-3 and MHC-II on CD4+ cells and tumor cells hinders CD4+ T cell proliferation and cytokine secretion, potentially aiding in tumor cell survival. (2) LAG-3 interaction with Galectin-3/LSECtin/FGL-1 on CD8+/NK cells in the tumor microenvironment suppresses CD8+/NK cell proliferation and cytotoxicity. (3) The binding of LAG-3 with MHC-II on Tregs and tumor cells/DCs enhances the stability and immunosuppressive function of Tregs while compromising DC maturation and immunostimulatory abilities through downstream MHC-II signaling. (4) The presence of sLAG-3 in the tumor microenvironment can disrupt the antigen presentation function of monocyte-derived DCs and impede the differentiation of monocytes into DCs.