Elucidating the immunosuppressive role of PMN-MDSCs via ferroptosis: impact on T cells in the tumor microenvironment 3369
Year: 2025
Type: article
Abstract: Description Immune evasion within the tumor microenvironment (TME) remains a significant obstacle to effective cancer treatment, with polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) playing a pivotal role in mediating this process. Here, we identify ferroptosis, a lipid peroxidation-dependent form of cell death, as a key driver of PMN-MDSC-mediated immunosuppression. Our study demonstrates that ferroptotic PMN-MDSCs release oxidized phospholipids, which directly impair T cell activation and functionality, reshaping the immune landscape to favor tumor progression. Through a combination of in vitro assays and in vivo models, we reveal that these oxidized lipid mediators act as potent suppressors of T cells. This mechanism uncovers a previously underexplored axis of lipid-mediated immunosuppression and offers a novel opportunity for therapeutic intervention. Targeting PMN-MDSC ferroptosis or its downstream lipid products could mitigate this suppression, reinvigorating T cell activity and enhancing anti-tumor immunity. Our findings contribute to the growing understanding of the immunosuppressive strategies employed by PMN-MDSCs and suggest that ferroptosis may represent a promising therapeutic target. Disrupting this pathway could help mitigate tumor-induced immune suppression and potentially improve the efficacy of immunotherapies. These insights into the interplay between lipid metabolism and immune regulation provide a valuable framework for future translational research. Funding Sources Supported by AstraZeneca Postdoctoral Research Funding. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
Source: The Journal of Immunology
Authors: Fatin Nurizzati Mohd Jaya, Dmitri Gabrilovich
Institution: AstraZeneca (United Kingdom)
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416448137
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