DCTPP1 drives immunosuppression and poor prognosis in breast cancer by promoting M2 macrophage polarization.

Breast cancer (BRCA) remains a major cause of cancer-related mortality among women, underscoring the need for reliable prognostic biomarkers and immunologically informed therapeutic targets. Deoxycytidine triphosphate pyrophosphatase 1 (DCTPP1) has been implicated in tumor progression, but its role in the BRCA immune microenvironment remains unclear. Here, we integrated multi-omics analyses, tissue microarray (TMA) profiling, and functional assays to investigate the clinical and immune significance of DCTPP1 in BRCA. DCTPP1 was upregulated at both the mRNA and protein levels, and high DCTPP1 expression was associated with adverse clinicopathological features and poor overall survival (OS), and remained an independent prognostic factor in multivariable analyses. Computational immune infiltration analyses indicated that elevated DCTPP1 expression was associated with an immunosuppressive microenvironment, characterized by increased M2 macrophage infiltration and reduced CD8⁺ T-cell and M1 macrophage signatures; these findings were corroborated by multiplex immunohistochemistry(mIHC) in a TMA cohort. In Transwell co-culture, DCTPP1 knockdown in MCF-7 cells shifted THP-1–derived macrophages toward an M1-like phenotype, increasing the proportion of CD11b⁺CD86⁺ cells while decreasing CD11b⁺CD206⁺ cells, and concomitantly upregulating CD86 and TNF-α while downregulating CD163 and CD206. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-39407-5.