Hematology · Gastroenterology · Oncology · 7 h ago
Mucosal CAR-T cells and inflammatory remodeling linked to enterocolitis after BCMA-targeted therapy
An observational biopsy study compared 10 patients with enterocolitis after ciltacabtagene autoleucel, seven CAR-T-treated controls without enterocolitis and 26 healthy volunteers. Findings linked enterocolitis to mucosal immune depletion and inflammatory remodeling; two affected patients improved after upadacitinib, providing preliminary support for further study.
- Biopsies compared 10 enterocolitis cases, seven treated controls and 26 volunteers.
- Enterocolitis involved mucosal immune depletion and multicompartment inflammatory remodeling.
- Two patients improved with upadacitinib; controlled efficacy evidence remains lacking.
A Nature Medicine study examined mucosal immune changes in enterocolitis associated with ciltacabtagene autoleucel, a B cell maturation antigen (BCMA)-targeted CAR-T therapy for multiple myeloma. Researchers used single-cell transcriptomics, flow cytometry and tissue imaging to analyze intestinal biopsies from 10 patients with enterocolitis, seven CAR-T-treated controls without enterocolitis and 26 healthy volunteers.
Enterocolitis was associated with profound depletion of mucosal B cells and plasma cells, expansion of highly cytotoxic CAR-T cells, and inflammatory remodeling involving myeloid, stromal and glial cells. Cell–cell communication analyses suggested a compensated mucosal state in treated controls, contrasting with telocyte-driven stromal niche dysfunction in affected patients. Interferon- and JAK–STAT-associated reprogramming was identified across stromal, endothelial and epithelial compartments.
These findings provide a mechanistic rationale for investigating JAK inhibition. Two patients treated with the selective JAK1 inhibitor upadacitinib experienced clinical, endoscopic and histologic improvement. However, the small observational cohort and two treatment observations do not establish causality or treatment efficacy. The supplied preview does not report quantitative response measures, follow-up duration or treatment safety outcomes.
Is this summary clinically accurate?
Help fellow clinicians: your rating sends inaccurate summaries straight to our editors.
Sign in to rate this summary →Source
Nature Medicine: Persistence of mucosal CAR-T cells and inflammatory remodeling in enterocolitis associated with BCMA CAR-T cell therapy ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.