biostudies-literatureLi YNational Natural Science Foundation of China (National Science Foundation of China)344https://www.ebi.ac.uk/biostudies/studies/S-EPMC11289284biostudies-literatureUnknown10(1)Breast cancer (BRCA) has become the most common type of cancer in women. Improving the therapeutic response remains a challenge. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a classic tumour suppressor with emerging new functions discovered in recent years, and myeloid PTEN loss has been reported to impair antitumour immunity. In this study, we revealed a novel mechanism by which myeloid PTEN potentially affects antitumour immunity in BRCA. We detected accelerated stress granule (SG) assembly under oxidative stress in PTEN-deficient bone marrow-derived macrophages (BMDMs) through the EGR1-promoted upregulation of TIAL1 transcription. PI3K/AKT/mTOR (PAM) pathway activation also promoted SG formation. ATP consumption during SG assembly in BMDMs impaired the phagocytic Cell death discoveryMyeloid PTEN loss affects the therapeutic response by promoting stress granule assembly and impairing phagocytosis by macrophages in breast cancer.PMC112892848217277582102905Pan YChen JFeng XDong MXu CWang GZhang RYu HQian XHua HLi YYang ZHan CfalseMyeloid PTEN loss affects the therapeutic response by promoting stress granule assembly and impairing phagocytosis by macrophages in breast cancer.Breast cancer (BRCA) has become the most common type of cancer in women. Improving the therapeutic response remains a challenge. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a classic tumour suppressor with emerging new functions discovered in recent years, and myeloid PTEN loss has been reported to impair antitumour immunity. In this study, we revealed a novel mechanism by which myeloid PTEN potentially affects antitumour immunity in BRCA. We detected accelerated stress granule (SG) assembly under oxidative stress in PTEN-deficient bone marrow-derived macrophages (BMDMs) through the EGR1-promoted upregulation of TIAL1 transcription. PI3K/AKT/mTOR (PAM) pathway activation also promoted SG formation. ATP consumption during SG assembly in BMDMs impaired the phagocytic 2024-01-01T00:00:00Z2024 Jul2026-06-01T16:19:56.195Z2025-04-19T07:04:32.142ZS-EPMC112892843908025510.1038/s41420-024-02094-0