Checkpoint inhibition-induced sicca: a type II interferonopathy?

Area of Science:

• Immunology
• Oncology
• Rheumatology

Background:

• Immune checkpoint inhibitors (ICIs) treat cancer but can cause immune-related adverse events.
• Sicca complaints, dry eyes and mouth, are a known side effect of ICI therapy.
• Some patients develop sicca symptoms meeting criteria for primary Sjögren's syndrome (pSS).

Purpose of the Study:

• To compare salivary gland (SG) dysfunction in patients receiving ICI therapy with primary Sjögren's syndrome (pSS).
• To analyze the immunological and histological differences in SG parenchyma.
• To explore potential new classifications and management strategies for ICI-induced SG dysfunction.

Main Methods:

• Review of literature on ICI-induced sicca syndrome and primary Sjögren's syndrome.
• Analysis of SG biopsy findings, focusing on immune cell infiltration and histological features.
• Comparison of clinical presentation, SG function, and ultrasound abnormalities.

Main Results:

• ICI-induced SG dysfunction shares sicca symptoms with pSS but exhibits distinct immunological characteristics.
• SG biopsies post-ICI show T-cell-dominated infiltration, unlike the B-cell dominance in pSS.
• Absence of germinal centers, lymphoepithelial lesions, and IgG plasma cells in ICI-treated SG parenchyma.

Conclusions:

• ICI-induced SG dysfunction may represent a novel interferonopathy, potentially driven by IFNγ.
• The distinct pathophysiology suggests that patients with ICI-induced 'pSS' may require different management than classical pSS patients.
• Further research is needed to confirm the interferonopathy hypothesis and guide treatment strategies.