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Abstract Number: 1409

Lack of Conventional Acinar Cells in the Salivary Gland Following Anti PD-L1 and anti-PD-1 Immune Checkpoint Inhibitor Therapy

Sarah Pringle1, Bert van der Vegt1, Xiaoyan Wang1, Nico van Bakelen1, Arjan Vissink1, Frans Kroese2 and Hendrika Bootsma2, 1UMCG, Groningen, 2University Medical Centre Groningen, Groningen, Netherlands

Meeting: ACR Convergence 2020

Keywords: autoimmune diseases, immunology, Sjögren's Syndrome, T Cell

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Session Information

Date: Sunday, November 8, 2020

Session Title: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Salivary glands (SGs) can be damaged by immune checkpoint inhibitor (ICI) therapy. In patients with ICI-induced SG dysfunction, 60% progress to fulfill the ACR-EULAR 2016 classification criteria for primary Sjögren’s syndrome (pSS), owing to immune foci in SGs and/or anti-SSA autoantibody positivity. We report the SG tissue analysis of 2 patients with SG dysfunction after treatment with anti PD-L1 and PD-1 ICIs, compared to that of a dry mouth (“sicca”) control and pSS patient.

Methods: Immunostaining for CD4, CD8, Keratin7 (K7), AQP5, Ki67, and PD-L1 was performed in two parotid SG biopsies from patients following ICI therapy, and in control and a pSS patient tissue. The first patient (male, 52 yrs) received fortnightly infusions of 10mg/kg durvalumab (anti-PD-L1 therapy), for non-small cell carcinoma (NSNLC). After 43 weeks (22 cycles) of treatment, the patient was not capable of producing stimulated or unstimulated whole saliva, and demonstrated SSA-positivity. The second patient (female, 74) received infusions of pembrolizumab (anti-PD-1) every 3 weeks for treatment of NSNLC, at a flat dose of 200mg. This patient was not capable of producing unstimulated whole saliva, and demonstrated reduced 0.12mL/min stimulated whole saliva production, after 15 weeks (5 cycles) of treatment. Both patients were SSA-positive following ICI treatment.

Results: In contrast to control and pSS tissue, following anti-PD-L1 and anti-PD-1 blockade, only few AQP5+, classically shaped acinar cell clusters were observed in the parotid SG after treatment with anti-PD-L1 and anti-PD-1 biologicals (Fig. 1a-c). The parenchyma was dominated by hybrid epithelial structures containing a mixture of AQP5+ (acinar cell marker) and K7+ (intercalated duct marker) cells (Figure 1d-f). AQP5+K7+ cells were also detected. Cells with this unusual phenotype are not seen in control/pSS tissue. More Ki67+ proliferating ID-like cells were detected following PD-L1 or PD-1 therapy, compared to control and pSS SGs. The SG post-PD-L1 and PD-1 therapy demonstrated focal and disperse lymphocytic sialadentitis. Infiltration was CD4+ T cell-rich, although CD8+ T cells were also present. CD4+ and CD8+ T cells were observed in-between and inside hybrid structures. CD20+ B-cells were infrequent. No germinal centers, lymphoepithelial lesions or antibody class-switching following ICI therapy were observed. PD-L1 expression was detected in the SG parenchyma following anti-PD-L1 therapy. 

Conclusion: Conventional SG acinar cells were lacking following both anti-PD-L1 and PD-1 ICI therapy. SGs demonstrated presence of hybrid intercalated duct-like structures. Understanding which mechanisms and dynamics underpin this aberrant parenchyma may be crucial to understand how SG dysfunction post-ICI therapy, and potentially other affected organs. Furthermore, although patients post-ICI therapy may fulfill the ACR-EULAR 2016 pSS criteria and demonstrate focal lymphocytic sialadentitis, the further histopathological characteristics do not resemble pSS.

Figure 1 a-c) H&E staining of the parotid salivary gland in sicca control, pSS and post-PD-L1 ICI therapy, showing lack of conventional acinar cell morphology following ICI treatment. d-f) AQP5 and Keratin 7 (K7) double immunostaining, showing presence of unusual hybrid mixed AQP5+K7+ cells post-PD-L1 therapy.


Disclosure: S. Pringle, None; B. van der Vegt, Visiopharm, 5; X. Wang, None; N. van Bakelen, None; A. Vissink, None; F. Kroese, Bristol-Myers Squibb, 2, 5, 8, Roche, 8, Janssen-Cilag, 8; H. Bootsma, Bristol-Myers Squibb, 2, 5, 8, Roche, 2, 5, Novartis, 5, 8, Medimmune, 5, Union Chimique Belge, 5.

To cite this abstract in AMA style:

Pringle S, van der Vegt B, Wang X, van Bakelen N, Vissink A, Kroese F, Bootsma H. Lack of Conventional Acinar Cells in the Salivary Gland Following Anti PD-L1 and anti-PD-1 Immune Checkpoint Inhibitor Therapy [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/lack-of-conventional-acinar-cells-in-the-salivary-gland-following-anti-pd-l1-and-anti-pd-1-immune-checkpoint-inhibitor-therapy/. Accessed April 16, 2021.
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