ANTI PD-L1 TREATMENT SKEWS PAROTID SALIVARY GLAND EPITHELIAL CELL COMPOSITION.
- Sarah Pringle, Netherlands
Abstract
Background and Aims
Background
The salivary glands (SGs) can be (severely) damaged by immune checkpoint inhibitor (ICI) therapy. In patients with ICI-induced SG dysfunction, 60% progress to fulfill classification criteria for primary Sjögren’s syndrome (pSS), owing to immune foci in SGs, and/or anti-SSA autoantibody positivity. Here we aim to understand how ICI treatment affects the SG epithelium.
Methods
Methods
Immunohistochemistry for CD4, CD8, cytokeratin 7 (CK7), AQP5, Ki67 and PD-L1 was performed in a parotid SG biopsy from a patient treated with anti-PD-L1, a control and a pSS patient.
Results
Results
Following PD-L1 blockade, dispersed and focal CD4+ T cell-rich infiltrate was observed. CD8+ T cells were also present. In this patient, no classical AQP5+ CK7- acinar cell clusters were observed (CK7 marks intercalated ducts, IDs). The parenchyma was dominated by aberrant epithelial ‘structures’ with ID-like morphology, containing a mixture of AQP5+CK7-, AQP5-CK7+ and AQP5+CK7+ cells (30 structures/mm2, 2/mm2 in control, 10/mm2 in pSS; Figure 1). 130 Ki67+ proliferating cells/mm2 in these epithelial structures were detected post-PD-L1 blockade (5/mm2 in control and 16/mm2 in pSS acinar+ID compartment). CD4+ and CD8+ T cells were observed in-between and inside aberrant structures following post-PD-L1 blockade. Immunostaining revealed that acinar cells in healthy SGs express PD-L1, suggesting an ability to interact directly with anti PD-L1 ICIs.
Conclusions
Conclusions
We show in this case study dramatically altered SG epithelium following anti-PD-L1 therapy, specifically presence of aberrant intercalated duct-like structures. The mechanism behind this dysfunction remains to be elucidated, and will be critical to understand checkpoint inhibitor induced development of sicca complaints.