Deoxythymidylate Kinase (DTYMK)-Driven Pyrimidine Hypermetabolism Is Associated with a Folate-Dependent Macrophage Programme in Triple-Negative Breast Cancer.

Gaoge Peng, Dequan Liu, Wucheng Zhu, Beibei Xin, Yi Wu, Yifeng Hou, Hefen Sun, Wei Jin

Abstract read

In one paragraph

Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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8 authors.

Gaoge PengKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Dequan LiuKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Wucheng ZhuKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.ORCID 0009-0006-7032-1784

Beibei XinKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Yi WuKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Yifeng HouKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Hefen SunKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Wei JinKey Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai 200032, China.ORCID 0009-0000-8456-3756

Funding

National Natural Science Foundation of China 82372961

6 · The paper itself

Abstract

Immune checkpoint blockade benefits only a minority of patients with triple-negative breast cancer (TNBC), and the tumour-intrinsic programmes that establish its immunosuppressive microenvironment remain poorly defined. Pyrimidine metabolism supplies nucleotides and one-carbon units in malignant cells, but whether it shapes the immune microenvironment is unknown. Integrating single-cell, bulk breast cancer transcriptomics with Xenium spatial transcriptomics, DTYMK knockdown, tumour-conditioned-medium co-culture and folate rescue, we found that pyrimidine pathway activity was elevated in the malignant epithelium of TNBC, within which we identified Epi4, a high-potency subpopulation coupling pyrimidine and folate metabolism and predicted to export folate. Furthermore, this folate was predicted to be taken up by FOLR2

Indexed as

Folic AcidMacrophagesNucleoside-Phosphate KinasePyrimidinesTriple Negative Breast NeoplasmsTumor-Associated MacrophagesAnimalsCell Line, TumorFemaleFolate Receptor 2Gene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingTumor MicroenvironmentFolate Receptor 2Folic AcidNucleoside-Phosphate KinasepyrimidinePyrimidinesDTYMKFOLR2+ macrophagesmetabolic crosstalkmulti-omicstriple-negative breast cancer

Identifiers

PMID42883873

DOI10.3390/ijms27198626

PMCPMC13665298

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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.