ArticleThe Journal of clinical investigation2018
SMAD4 promotes TGF-β-independent NK cell homeostasis and maturation and antitumor immunity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
55 citing papers in PubMed, 91 citations in OpenAlex.
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- Role of PRDM1 in natural killer cells.Molecular biology reports · 2026Review
- SKI is critical to counter TGF-β signaling to promote T cell function and autoimmunity.Science advances · 2026Article
- Natural Killer Cell Immunotherapy in Solid Tumors: Microenvironmental Obstacles and Translational 3D Models.Biology · 2026Review
- Bioinformatics-driven genome-wide identification of viral miRNAs in high spillover bat coronaviruses and their target genes in human.Archives of microbiology · 2026Article
- SMAD7 drives natural killer cell antitumor activity through canonical TGF-β blockade and non-canonical transcriptional activation of STAT5A.Journal for immunotherapy of cancer · 2026Article
- Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transcriptional networks weaving natural killer anti-tumor immune response.Molecular cancer · 2026Review
- Aligned cross-modal integration and regulatory heterogeneity characterization of single-cell multiomic data with deep contrastive learning.Genome medicine · 2026Article
- Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.Journal of molecular cell biology · 2026Article
- Oncolytic adenovirus encoding a TGF-β inhibitor synergizes with PD-1 blockade to potentiate NK cell cytotoxicity against NSCLC.Frontiers in immunology · 2026Article
- The Role of Fibroblasts in Melanoma Development: From Tumor Microenvironment Remodeling to Pre-Metastatic Niche Formation.International journal of molecular sciences · 2025Review
- scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL.Cell reports. Medicine · 2025Article
- MicroRNA-767-5p promotes metastasis but improves chemotherapeutic and radiotherapeutic sensitivity of osteosarcoma.BMC cancer · 2025Article
- Overcoming TGFβ and activin A suppression boosts NK cell antitumor function.Nature immunology · 2025Article
- Enhancing human NK cell antitumor function by knocking out SMAD4 to counteract TGFβ and activin A suppression.Nature immunology · 2025Article
- NKp46 enhances type 1 innate lymphoid cell proliferation and function and anti-acute myeloid leukemia activity.Nature communications · 2025Article
- Recent advances in therapeutic use of transforming growth factor-beta inhibitors in cancer and fibrosis.Frontiers in oncology · 2025Review
- Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
SMAD4 is the only common SMAD in TGF-β signaling that usually impedes immune cell activation in the tumor microenvironment. However, we demonstrated here that selective deletion of Smad4 in NK cells actually led to dramatically reduced tumor cell rejection and augmented tumor cell metastases, reduced murine CMV clearance, as well as impeded NK cell homeostasis and maturation. This was associated with a downregulation of granzyme B (Gzmb), Kit, and Prdm1 in Smad4-deficient NK cells. We further unveiled the mechanism by which SMAD4 promotes Gzmb expression. Gzmb was identified as a direct target of a transcriptional complex formed by SMAD4 and JUNB. A JUNB binding site distinct from that for SMAD4 in the proximal Gzmb promoter was required for transcriptional activation by the SMAD4-JUNB complex. In a Tgfbr2 and Smad4 NK cell-specific double-conditional KO model, SMAD4-mediated events were found to be independent of canonical TGF-β signaling. Our study identifies and mechanistically characterizes unusual functions and pathways for SMAD4 in governing innate immune responses to cancer and viral infection, as well as NK cell development.
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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.