Immune activity in Merkel cell carcinoma

Area of Science:

• Oncology
• Immunology
• Dermatology

Background:

• Merkel cell carcinoma (MCC) is an aggressive skin cancer with poorly understood pathogenesis, often affecting the elderly.
• Despite its malignancy, MCC can undergo spontaneous regression, suggesting a significant role for the tumor immune microenvironment.
• Current immune checkpoint blockade therapies show limited efficacy in about half of advanced MCC cases, necessitating novel treatment strategies.

Purpose of the Study:

• To review the evidence on the immune activity and immunological biomarkers of Merkel cell carcinoma.
• To introduce a novel classification system for MCC based on its immune activity.
• To explore the potential of this classification in predicting response to immunotherapy.

Main Methods:

• Literature review of studies investigating MCC pathogenesis, immune activity, and response to therapy.
• Analysis of existing data on immunological biomarkers in MCC.
• Proposal of a new MCC classification integrating programmed death ligand 1 and glucose-6-phosphate dehydrogenase.

Main Results:

• MCC demonstrates high immunosensitivity, contributing to its peculiar behaviors like spontaneous regression.
• Programmed death ligand 1 (PD-L1) is a prognostic factor and predictor of immune checkpoint inhibitor efficacy.
• Glucose-6-phosphate dehydrogenase (G6PD) emerges as a promising novel biomarker for MCC.

Conclusions:

• Understanding MCC immunokinetics is crucial for advancing cancer immunotherapy.
• A new classification combining PD-L1 and G6PD may stratify MCC based on immune status.
• This classification warrants further evaluation for predicting immune checkpoint blockade therapy efficacy and guiding treatment selection.