The Novel Checkpoint Target Lymphocyte-Activation Gene 3 Is Highly Expressed in Cutaneous Squamous Cell Carcinoma

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Lymphocyte activation-gene 3 (LAG-3) is an emerging immune checkpoint molecule.
• Understanding LAG-3 expression in cutaneous squamous cell carcinoma (cSCC) is crucial for prognosis and therapy.
• LAG-3 plays a key role in regulating T-cell responses.

Purpose of the Study:

• To define the expression pattern of LAG-3 in cSCC.
• To investigate the role of LAG-3 in cSCC prognosis and therapy.
• To compare LAG-3 expression with programmed cell death protein -1 (PD-1) in cSCC.

Main Methods:

• Isolation of CD8+ T lymphocytes from cSCC tumors.
• Single-cell RNA sequencing for LAG-3 and PD-1 expression analysis.
• NanoString technology for evaluating LAG-3 mRNA expression in formalin-fixed, paraffin-embedded tissues.

Main Results:

• LAG-3 expression was higher than PD-1 in CD8+ tumor-infiltrating lymphocytes (50.8% vs 35.2%).
• LAG-3 mRNA expression was significantly elevated in cSCC tumors compared to normal skin (approx. 8-fold in immunocompetent-associated SCC, 2-fold in transplant-associated SCC).
• LAG-3 mRNA was 7.2-fold higher in T2a stage cSCC compared to normal skin.

Conclusions:

• LAG-3 is expressed on cSCC-infiltrating T lymphocytes at a higher percentage than PD-1.
• LAG-3 mRNA expression is significantly elevated in cSCC tumors.
• Further studies are warranted to define LAG-3's role as an immune biomarker and therapeutic target in cSCC.