LAG-3: new biomarker under investigation in immuno-oncology

LAG-3, or lymphocyte activation gene 3, is a prominent new biomarker currently being researched in immuno-oncology. LAG-3 is an immune checkpoint receptor protein located on the cell surface of certain T cells involved in the immune response.¹ LAG-3 expression is associated with T cell desensitization, which results in the progressive loss of the ability to trigger an immune response.² In cancer, LAG-3–expressing cells cluster at tumor sites.^3,4  

Preclinical studies have shown that the inhibition of LAG-3 improves T cell ability to coordinate immune response.⁵ Additionally, combining the inhibition of LAG-3 with other immune pathways (eg, anti-programmed cell death-1 [PD-1], anti-PD-1 ligand expression [PD-L1] checkpoint inhibitors) in order to promote anti-tumor activity is another therapeutic approach currently under investigation.⁶ 

A search of LAG-3 in the 2019 ASCO Abstracts database revealed multiple studies on this promising biomarker are underway. 

References 

1. Durham NM, Nirschl CJ, Jackson CM, et al. Lymphocyte activation gene 3 (LAG-3) modulates the ability of CD4 T-cells to be suppressed in vivo. PLoS One. 2014 Nov 5;9(11):e109080.
2. Goldberg MV, Drake CG. LAG-3 in cancer immunotherapy. Curr Top Microbiol Immunol. 2011; 344:269–278. 
3. Huang CT, Workman CJ, Flies D, et al. Role of LAG-3 in regulatory T cells. Immunity. 2004; 21(4):503-513.     
4. Camisaschi C, Casati C, Rini F, et al. LAG-3 expression defines a subset of CD4+ CD25high Foxp3+ regulatory T cells that are expanded at tumor sites. J Immunol. 2010; 184(11):6545-6551.     
5. Grosso JF, Kelleher CC, Harris TJ, et al. LAG-3 regulates CDS+ T cell accumulation and effector function in murine self and tumor-tolerance systems. J Clin Invest. 2007;117(11):3383-3392.
6. Lichtenegger FS, Rothe M, Schnorfeil FM, et al. Targeting LAG-3 and PD-1 to enhance t cell activation by antigen-presenting cells. Front Immunol. 2018 Feb 27;9:385.