Dataset Information

Cancer cell-derived arginine fuels polyamine biosynthesis in tumor-associated macrophages to promote immune evasion

ABSTRACT: Cancer cell metabolic reprogramming reshapes the tumor microenvironment (TME) into a pro-tumor niche. Arginine metabolism plays complex roles in regulating tumor progression through metabolic cross-feeding among various cell types within the TME, but the primary intercellular communication dominating the collective impact of arginine on tumor progression remains unclear. Here, we investigated the role of arginine metabolism in breast cancer progression using clinical analysis, single-cell RNA sequencing data analysis, and in vivo animal models. We found that the metabolic interplay between cancer cells and macrophages exerts a predominant influence on breast cancer progression mediated by arginine metabolism. Breast cancer cells act as the major source of arginine within the TME, where this tumor-derived arginine fosters a pro-tumor shift in tumor-associated macrophages (TAMs), leading them to suppress the anti-tumor activity of CD8+ T cells. Notably, this cancer cell-macrophage interaction overrides the stimulatory effect of arginine on the anti-tumor capability of CD8+ T cells. Mechanistically, polyamines derived from arginine metabolism mediate TAM polarization via TDG-mediated DNA demethylation, driven by p53 signaling. Importantly, inhibiting the arginine-polyamine-TDG axis across cancer cells to macrophages effectively suppresses breast cancer growth by modulating the immune microenvironment, suggesting therapeutic potential in targeting this axis for breast cancer therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE285794 | GEO | 2025/06/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage of HPV infection, progresses to intraepithelial neoplasia, and then develops into invasion and metastasis. Determining the complexity of tumor microenvironment (TME) can deepen our understanding of lesion progression and provide novel therapeutic strategies for CC. We performed the single-cell RNA sequencing on the normal cervix, intraepithelial neoplasia, primary tumor and metastatic lymph node tissues to describe the composition, lineage, and functional status of immune cells and mesenchymal cells at different stages of CC progression. A total of 59913 single cells were obtained and divided into 9 cellular clusters, including immune cells (T/NK cells, macrophages, B cells, plasma cells, mast cells and neutrophils) and mesenchymal cells (endothelial cells, smooth muscle cells and fibroblasts). Our results showed that there were distinct cell subpopulations in different stages of CC. High-stage intraepithelial neoplasia (HSIL) tissue exhibited a low, recently activated TME, and it was characterized by high infiltration of tissue-resident CD8 T cell, effector NK cells, Treg, DC1, pDC, and M1-like macrophages. Tumor tissue displayed high enrichment of exhausted CD8 T cells, resident NK cells and M2-like macrophages, suggesting immunosuppressive TME. Metastatic lymph node consisted of naive T cell, central memory T cell, circling NK cells, cytotoxic CD8+ T cells and effector memory CD8 T cells, suggesting an early activated phase of immune response. This study is the first to delineate the transcriptome profile of immune cells during CC progression using single-cell RNA sequencing. Our results indicated that HSIL exhibited a low, recently activated TME, tumor displayed immunosuppressive statue, and metastatic lymph node showed early activated phase of immune response. Our study enhanced the understanding of dynamic change of TME during CC progression and has implications for the development of novel treatments to inhibit the initiation and progression of CC.

Dataset Information

Cancer cell-derived arginine fuels polyamine biosynthesis in tumor-associated macrophages to promote immune evasion

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets