Abstract
Background: Cancer patients receiving antibodies abrogating immune checkpoint pathways may develop a diverse array of immune-related adverse events (irAEs), of which lichenoid dermatitis (LD) is the most common. The mechanism driving the emergence of these irAEs remain understudied, underscoring a critical need to determine the unique gene expression profiles and immune composition in LD—irAE. Methods: LD—irAE (n = 3) and benign lichenoid keratosis (BLK) control (n = 3) were profiled with NanoString nCounter PanCancer Immune Profiling Panel interrogating the mRNA levels of 770 genes. Immunohistochemical (IHC) studies (n = 14 samples) for CD14, CD16, T-Bet, Gata-3, and FoxP3 were further evaluated using Aperio digital image analysis. Results: The LD—irAE showed downregulation of 93 mRNA transcripts (P < 0.05) and upregulation of 74 mRNA transcripts (P < 0.04) including toll-like receptor (TLR) 2 and TLR4 (P < 0.05). CD14+ and CD16+ monocytes quantified by IHC (H-score) were higher in LD—irAE than in the BLK control (P < 0.05). The immune composition of LD—irAE exhibited higher numbers of T-Bet+ (Th1) cells compared with Gata-3+ (Th2) cells (P = 0.016) and lower numbers of FoxP3 (T regulatory) cells (P = 0.008). Conclusions: LD—irAE exhibited activation of CD14/TLR innate immune response with increased CD14+ and CD16+ monocytes compared with BLK control. CD14/TLR signaling may drive the development of LD—irAE.
Original language | English (US) |
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Pages (from-to) | 627-636 |
Number of pages | 10 |
Journal | Journal of cutaneous pathology |
Volume | 46 |
Issue number | 9 |
DOIs | |
State | Published - 2019 |
Keywords
- CD14 and CD16 monocytes
- checkpoint inhibitor
- gene expression
- immune-related adverse events
- lichenoid dermatitis
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Histology
- Dermatology
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