ArticleMolecular therapy. Oncology2025
Intrinsic immunosuppressive features of monocytes suppress CAR-T19 through IL-1 pathway modulation in mantle cell lymphoma.
Article in Molecular therapy. Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- TRAIL splice variant TRAILshort disrupts T cell receptor signaling and promotes immune tolerance in vivo.The Journal of clinical investigation · 2026Article
- [Advances in single cell omics applications in mantle cell lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Breaking the resistance barrier: synergistic evolution of CAR-T cells and bispecific antibodies in the era of precision immuno-oncology.Frontiers in immunology · 2026Review
- Expanding Immunotherapy Beyond CAR T Cells: Engineering Diverse Immune Cells to Target Solid Tumors.Cancers · 2025Review
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
CD19-targeted chimeric antigen receptor T cells (CAR-T19) have shown remarkable success in B cell malignancies, but most patients relapse within 1-2 years. Here, we identified interleukin-1 (IL-1) receptor antagonist (IL-1ra) as a mediator of M2-like macrophage-derived inhibition of CAR-T19 in mantle cell lymphoma (MCL), as well as a potential target to enhance CAR-T19 efficacy. In preclinical models that recapitulated interactions between tumor, macrophages, and T cells, we demonstrated that M2-derived IL-1ra impairs IL-1 signaling and functions of CAR-T19. These findings were validated using clinical samples from the ZUMA-2 trial that led to the FDA approval of CAR-T19 in MCL. Single-cell RNA sequencing of CAR-T19 products and baseline myeloid cells indicated downregulated IL-1β production, enriched immunosuppressive phenotypes, and IL-1ra upregulation in the non-responder monocytes, as well as impaired IL-1β signaling and T cell functions in the non-responder CAR-T19 products. Furthermore, our preclinical studies of IL-1β showed enhanced CAR-T antitumor activities. Collectively, these data present a potential role for IL-1 signaling and IL-1ra in CAR-T19 failure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.