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Complex interaction of tumor-derived factors instructs the niche specific phenotypes of tumor-associated macrophages (in vitro human macrophage RNA-Seq)

GSE301110 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2025/08/03 Platform GPL24676
Summary
Despite the pivotal role of tumor-associated macrophages (TAMs) in modulating anti-tumor immunity, the conserved patterns and molecular determinates for the formation of diverse TAM subsets remain largely elusive. In this study, we uncovered the exclusive distribution of pro-angiogenic and MHC-II programs of TAMs are well-conserved, and identified key genes and pathways required for macrophage polarization by tumor cells by CRISPR screen. Notably, we demonstrated that multiple TAM phenotypes were mainly shaped by the synergistic and antagonistic interactions between GM-CSF, PGE2, and lactic acid. We further found the inactivation of Adar, an RNA-editing enzyme, reprograms TAMs into an ISG+ phenotype characterized by the high expression of immune stimulatory genes, thereby enhancing the anti-tumor immune response. Thus, our study illuminates the molecular principles underlying the generation and rewiring of TAM functional phenotypes.
Published in
Functional Genetic Screens Reveal Key Pathways Instructing the Molecular Phenotypes of Tumor-Associated Macrophages
Lu Y, Luo C, Huang L et al. · Cancer immunology research 2025 · PMID 40906823 · doi:10.1158/2326-6066.CIR-25-0488
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Direct links to NCBI, no account and no request form: the whole study as GSE301110_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1283951 and SRA study SRP595900. Searching any of these in the dataset finder brings you back here.

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