biostudies-literatureUnknown16(12)Yang XSpermidine metabolism influences tumor progression and anti-tumor immunity, thereby affecting treatment sensitivity. However, the precise role and therapeutic potential of spermidine in breast cancer remain unclear. Integrated multi-omics analyses (bulk and single-cell RNA sequencing) revealed a significant positive correlation between intratumoral spermidine abundance and immunophenotypic markers of CD8⁺ T cell infiltration and activation (GZMB⁺CD8⁺ T cells). Immunohistochemical and multiplexed immunohistochemistry validation (IHC/mIHC) demonstrated that breast cancer specimens with elevated spermidine production exhibited increased numbers of activated CD8⁺ T cells. Exogenous supplementation with spermidine promoted CD8⁺ T cell activation directly. Furthermore, supplementing spermidine <i>in vivo</i> promoted anti-tumor immune responses and enhanced sensitivity to anti-PD-1 immunotherapy combined with chemotherapy. Our findings indicate that boosting spermidine metabolism is a promising strategy to reinvigorate CD8⁺ T cell function and improve the efficacy of checkpoint blockade immunotherapy.Journal of Cancer3684-3695https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435280biostudies-literatureSpermidine potentiates anti-tumor immune responses and immunotherapy sensitivity in breast cancer.PMC12435280Yang XGao BWang RFeng YZeng XChen HZeng WHuang PfalseSpermidine potentiates anti-tumor immune responses and immunotherapy sensitivity in breast cancer.Spermidine metabolism influences tumor progression and anti-tumor immunity, thereby affecting treatment sensitivity. However, the precise role and therapeutic potential of spermidine in breast cancer remain unclear. Integrated multi-omics analyses (bulk and single-cell RNA sequencing) revealed a significant positive correlation between intratumoral spermidine abundance and immunophenotypic markers of CD8⁺ T cell infiltration and activation (GZMB⁺CD8⁺ T cells). Immunohistochemical and multiplexed immunohistochemistry validation (IHC/mIHC) demonstrated that breast cancer specimens with elevated spermidine production exhibited increased numbers of activated CD8⁺ T cells. Exogenous supplementation with spermidine promoted CD8⁺ T cell activation directly. Furthermore, supplementing spermidine <i>in vivo</i> promoted anti-tumor immune responses and enhanced sensitivity to anti-PD-1 immunotherapy combined with chemotherapy. Our findings indicate that boosting spermidine metabolism is a promising strategy to reinvigorate CD8⁺ T cell function and improve the efficacy of checkpoint blockade immunotherapy.2025-01-01T00:00:00Z20252026-06-02T05:23:32.103Z2026-04-14T03:13:57.199ZS-EPMC124352804095911010.7150/jca.113235