Immunology and targeted therapy in Castleman disease.
Shinichiro TsunodaTakuya HaradaYoshikane KikushigeTadamitsu KishimotoKazuyuki YoshizakiPublished in: Expert review of clinical immunology (2024)
The pathogenesis of MCD has been implicated in the activation of the Janus kinase (JAK)-transcriptional signaling activator (STAT) 3 pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt/mechanical target of rapamycin (mTOR) signaling pathway. iMCD-TAFRO (thrombocytopenia, anasarca, fever/elevated CRP, reticulin myelofibrosis/renal dysfunction, organ enlargement) is resistant to IL-6 inhibitors, and cyclosporine and mTOR inhibitors are sometimes effective. JAK inhibitors and mTOR inhibitors may be therapeutic agents for iMCD. Recently, we have shown that peripheral helper T (Tph) cell abnormalities are at the core of iMCD pathogenesis. Therapies targeting chemokine (C-X-C motif) ligand 13 (CXCL13) produced by Tph cells and blocking the Tph-CXCL13-B cell pathway may satisfy unmet need in refractory cases.
Keyphrases
- pi k akt
- signaling pathway
- cell proliferation
- cell cycle arrest
- induced apoptosis
- protein kinase
- gene expression
- oxidative stress
- cell death
- single cell
- transcription factor
- dendritic cells
- endoplasmic reticulum stress
- drug delivery
- mesenchymal stem cells
- inflammatory response
- immune response
- heat shock
- chemotherapy induced