Quantitative proteomics of tissue infiltrating T cells from CRC patients identified Lipocalin-2 induces T cell apoptosis and promotes tumor cell proliferation by iron efflux

In this study, we analyzed the protein expression pattern of the infiltrating T cells isolated from CRC patients using quantitative proteomics. CD4+ and CD8+ T cells were isolated from clinical samples and labeled by TMT reagents, and the DEPs were quantified by mass spectrometry. The T cell proteome profiling revealed dysfunctions in these tumor-infiltrating T cells. Specifically, anti-tumor immunity was suppressed due to differentially expressed metal ion transporters and immunity regulators. For the first time, Lipocalin-2 (LCN2) was shown to be significantly up-regulated in CD4+ T cells. Quantitative proteomic analysis of LCN2-overexpressed Jurkat cells showed that LCN2 damaged T cells by changes in iron transport. LCN2 induced T cell apoptosis by reducing cellular iron concentration; moreover, the iron that was transported to the tumor microenvironment aided tumor cell proliferation, promoting tumor development. Meanwhile, LCN2 also influenced tumor progression through immune cytokines and cholesterol metabolism. Our results demonstrated that LCN2 has immunosuppressive functions that can promote tumor development; therefore, it is a potential immunotherapy target for CRC.PMID:38072118 | DOI:10.1016/j.mcpro.2023.100691
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research