biostudies-literaturePuttock EHCancer Research UK2514https://www.ebi.ac.uk/biostudies/studies/S-EPMC10185550biostudies-literatureUnknown14(1)Recent studies have shown that the tumor extracellular matrix (ECM) associates with immunosuppression, and that targeting the ECM can improve immune infiltration and responsiveness to immunotherapy. A question that remains unresolved is whether the ECM directly educates the immune phenotypes seen in tumors. Here, we identify a tumor-associated macrophage (TAM) population associated with poor prognosis, interruption of the cancer immunity cycle, and tumor ECM composition. To investigate whether the ECM was capable of generating this TAM phenotype, we developed a decellularized tissue model that retains the native ECM architecture and composition. Macrophages cultured on decellularized ovarian metastasis shared transcriptional profiles with the TAMs found in human tissue. ECM-educated macropNature communicationsExtracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis.PMC10185550A27947Maniati EButterworth CPearce OMTManni MBurger Ramos MGauthier VCutillas PHirani PManiscalco GLiu YRajeeve VPuttock EHTyler EJLaubli HPozzobon MRastrick JLockley MPeerani ETrevisan CWhite AfalseExtracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis.Recent studies have shown that the tumor extracellular matrix (ECM) associates with immunosuppression, and that targeting the ECM can improve immune infiltration and responsiveness to immunotherapy. A question that remains unresolved is whether the ECM directly educates the immune phenotypes seen in tumors. Here, we identify a tumor-associated macrophage (TAM) population associated with poor prognosis, interruption of the cancer immunity cycle, and tumor ECM composition. To investigate whether the ECM was capable of generating this TAM phenotype, we developed a decellularized tissue model that retains the native ECM architecture and composition. Macrophages cultured on decellularized ovarian metastasis shared transcriptional profiles with the TAMs found in human tissue. ECM-educated macrop2023-01-01T00:00:00Z2023 May2025-04-25T22:38:41.667Z2025-04-06T09:05:33.716ZS-EPMC101855503718869110.1038/s41467-023-38093-5