ADVANCE ONLINE PUBLICATION

RESEARCH HIGHLIGHTS

Targeting NNMT in fibroblasts reawakens T cells and restores antitumor immunity

Moumita Sarkar¹ , Yi Jiang¹ , Raghu Kalluri^1,2,3,4,*

¹Department of Cancer Biology, Metastasis Research Center, UT MD Anderson Cancer Center, Houston, TX, USA
²Department of Bioengineering, Rice University, Houston, TX, USA
³Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
⁴Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA
* Correspondence: Raghu Kalluri(rkalluri@mdanderson.org)

The tumor stroma, long considered a therapeutic challenge due to its heterogeneity, is now revealed to harbor a unifying vulnerability. In a recent Nature study, Heide et al. identify nicotinamide N-methyltransferase (NNMT) as a master metabolic-epigenetic regulator across cancer-associated fibroblast (CAF) subtypes that drives immune suppression, and report that pharmacological inhibition of NNMT reprograms fibroblasts, curtails suppressive myeloid recruitment, and synergizes with immune checkpoint blockade — unveiling a promising strategy to rewire the tumor microenvironment for durable antitumor immunity.

https://doi.org/10.1038/s41422-025-01181-w

FULL TEXT | PDF

Browse 12