Multi-omics analysis revealed that patients with immune checkpoint inhibitor-induced thrombocytopenia exhibited distinct gut microbiota profiles and systemic arginine depletion, suggesting that disruptions in arginine and associated metabolic pathways are associated with ICIs-TCP pathogenesis.
Key Findings
Results
Patients with ICIs-TCP exhibited distinct gut microbiota profiles compared to those without ICIs-TCP.
Study compared cancer patients with ICIs-TCP (n=8) versus without ICIs-TCP (n=8) using fecal metagenomic shotgun sequencing.
ICIs-TCP patients showed increased abundance of Segatella, Prevotella, and Clostridium.
ICIs-TCP patients showed depletion of Bacteroides and Roseburia.
Microbial composition was assessed via fecal metagenomic shotgun sequencing.
Results
Functional analysis of gut microbiota revealed significant downregulation of metabolic pathways in ICIs-TCP patients.
Downregulated pathways included arginine biosynthesis.
Alanine, aspartate, and glutamate metabolism pathways were also significantly downregulated.
These functional changes were identified through metagenomic functional pathway analysis.
Results
Plasma metabolomics identified reduced arginine levels and disruptions in key amino acid and energy metabolism pathways in ICIs-TCP patients.
Arginine levels were reduced in the plasma of ICIs-TCP patients.
Findings suggest systemic arginine depletion in ICIs-TCP.
Disruptions extended to key amino acid and energy metabolism pathways beyond arginine alone.
Plasma metabolomics analysis was used to identify systemic metabolic changes.
Results
Proteomic analysis demonstrated down-regulation of folate hydrolase 1 (FOLH1) in ICIs-TCP patients.
FOLH1 is described as a key enzyme in glutamate metabolism.
Down-regulation of FOLH1 implicates metabolic dysregulation in TCP pathogenesis.
FOLH1 changes were identified through plasma proteomics analysis.
This finding links glutamate metabolism disruption to ICIs-TCP.
Conclusions
The study identifies arginine depletion and associated metabolic disruptions as a potential therapeutic target for mitigating ICIs-TCP risk.
ICIs-TCP is described as a rare immune-related adverse event (irAE).
The physiological changes underlying ICIs-TCP were previously incompletely elucidated.
Multi-omics approach integrated gut microbiome, plasma metabolomics, and plasma proteomics data.
Authors suggest arginine and associated metabolic pathways 'may represent a potential therapeutic target for mitigating TCP risk in patients receiving ICIs.'
Xu B, Liu P, Yan N, Wang T, Liu L, Cheng Y. (2026). Multi-omics insights into gut microbial dysbiosis and metabolic alterations in immune checkpoint inhibitor-induced thrombocytopenia.. Immunotherapy. https://doi.org/10.1080/1750743X.2026.2618937