Tissue and circulating PD-L2: moving from health and immune-mediated diseases to head and neck oncology

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• The Programmed cell death protein 1 (PD-1)/PD-Ligands (Ls) axis is a key target for immune-checkpoint inhibitors (ICIs).
• Research has predominantly focused on PD-L1, leaving PD-L2 under-investigated.
• Emerging evidence suggests PD-L2 expression in head and neck malignancies, including head and neck squamous cell carcinoma (HNSCC) and salivary gland cancers (SGCs).

Purpose of the Study:

• To review the biological significance of PD-L2.
• To analyze PD-L2 tissue expression, binding interactions (PD-1 and RGMb), and its role in immune responses.
• To identify PD-L2 as a potential predictive biomarker in head and neck cancers.

Main Methods:

• Literature review focusing on PD-L2 biology and expression in head and neck cancers.
• Analysis of reported PD-L2 expression rates and clinical correlates across various head and neck cancer histotypes.
• Review of the biology of soluble PD-L2 and its potential as a biomarker.

Main Results:

• PD-L2 expression is relevant in HNSCC and SGCs.
• PD-L2 plays a role in both physiological and anti-cancer immune responses.
• Clinical correlates of PD-L2 expression vary among different head and neck cancer types.
• Soluble PD-L2 has potential as a circulating prognostic and/or predictive biomarker.

Conclusions:

• PD-L2 is an important, yet under-investigated, factor in head and neck cancers.
• Understanding PD-L2's role is crucial for developing effective immune-based therapies.
• Soluble PD-L2 warrants further investigation as a non-invasive biomarker for patient stratification and treatment guidance.