The Next-Generation Immune Checkpoint LAG-3 and Its Therapeutic Potential in Oncology: Third Time's a Charm.
Quentin LecocqMarleen KeyaertsNick DevoogdtKarine BreckpotPublished in: International journal of molecular sciences (2020)
The blockade of immune checkpoints (ICPs), such as cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed death-1 (PD-1) and its ligand (PD-L1), has propelled the field of immuno-oncology into its current era. Drugs targeting these ICPs have improved clinical outcome in a number of patients with solid and hematological cancers. Nonetheless, some patients have no benefit from these ICP-blocking therapies. This observation has instigated research into alternative pathways that are responsible for the escape of cancer cells from anti-cancer immune responses. From this research, a number of molecules have emerged as promising therapeutic targets, including lymphocyte activating gene-3 (LAG-3), a next-generation ICP. We will review the current knowledge on the biological activity of LAG-3 and linked herewith its expression on activated immune cells. Moreover, we will discuss the prognostic value of LAG-3 and how LAG-3 expression in tumors can be monitored, which is an aspect that is of utmost importance, as the blockade of LAG-3 is actively pursued in clinical trials.
Keyphrases
- clinical trial
- poor prognosis
- immune response
- palliative care
- end stage renal disease
- healthcare
- newly diagnosed
- ejection fraction
- gene expression
- randomized controlled trial
- peritoneal dialysis
- signaling pathway
- papillary thyroid
- prognostic factors
- genome wide
- dna methylation
- cancer therapy
- dendritic cells
- transcription factor
- young adults
- open label
- patient reported
- squamous cell
- childhood cancer
- double blind
- phase iii