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.
Although the coronavirus pandemic has been the defining global health crisis of our time, public health officials have been sounding the alarm of another ominous threat for years: an impending antimicrobial resistance (AMR) crisis.
Antibiotics in dermatology are often used for prolonged courses in the treatment of skin and soft tissue infections and common inflammatory skin conditions, increasing the risk of microbiome alteration and antibiotic-related adverse effects, all while exerting consequential selective pressures on both pathogenic and bystander bacteria. In this review, we hope to raise awareness of the crisis of AMR and review the resistance concerns related to dermatology-relevant bacterial pathogens.
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