CD24 in Melanoma: Biomarker, Innate Immune Checkpoint and Emerging Therapeutic Target

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Advanced melanoma treatment has been revolutionized by immune checkpoint inhibitors (ICIs).
• However, primary and acquired resistance to ICIs remains a significant clinical challenge.
• Emerging evidence points to innate immune suppression and stem-like melanoma cell states as key drivers of resistance.

Purpose of the Study:

• To review the role of CD24 in melanoma, focusing on its function as a regulator of tumour-intrinsic and tumour-extrinsic processes.
• To explore the CD24-Siglec-10 axis as an innate immune checkpoint in melanoma.
• To discuss CD24 as a biomarker and therapeutic target for melanoma.

Main Methods:

• Literature review synthesizing evidence on CD24 structure, regulation, and function in melanoma.
• Analysis of CD24's role in phenotypic plasticity, stem-like populations, and therapy resistance.
• Examination of the CD24-Siglec-10 axis in modulating the tumour microenvironment and immune cell function.

Main Results:

• CD24 supports melanoma phenotypic plasticity and sustains stem-like populations via SOX2/STAT3 pathways.
• CD24 promotes resistance to BRAF-targeted and cytotoxic therapies.
• The CD24-Siglec-10 axis acts as an innate immune checkpoint, suppressing anti-tumour immunity and creating 'cold' tumours.

Conclusions:

• CD24 is a crucial regulator of aggressive, therapy-resistant melanoma states.
• CD24 and its axis represent promising biomarkers and therapeutic targets for melanoma.
• Targeting the CD24 axis, in combination with existing therapies, could overcome resistance and enhance immunotherapy efficacy.