Gene expression profiling of lichenoid dermatitis immune-related adverse event from immune checkpoint inhibitors reveals increased CD14+ and CD16+ monocytes driving an innate immune response.
J Cutan Pathol
; 46(9): 627-636, 2019 Sep.
Article
en En
| MEDLINE
| ID: mdl-30883858
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Monocitos
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Erupciones Liquenoides
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Erupciones por Medicamentos
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Inmunidad Innata
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Antineoplásicos
Tipo de estudio:
Observational_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Cutan Pathol
Año:
2019
Tipo del documento:
Article