{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334550/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334550"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"TNFR1 expression on cancer cells is critical for immune escape shaping an immunosuppressive tumor microenvironment","description":"TNFα is an proinflammatory cytokine that can mediate immunosuppressive effects in cancer. Tumors in which we silenced TNFR1 by CRISPR/Cas9 showed disability of the TNFR1 KO variants to engraft in immunocompetent hosts, whilst engraftment in immunodeficient or CD8 T lymphocyte-depleted mice was preserved. The mechanism was mediated by secondary chemotactic inflammatory mediators elicited by TNFα in the malignant cells themselves. As a result, TNFR1 KO variants recruited drastically fewer myeloid-derived suppressor cells into the tumor microenvironment, thus explaining the immune escape of the WT variants. Interestingly, small amounts of TNFR1-sufficient tumor cells co-engrafted with the TNFR1 KO variants rescued tumorigenicity in the same tumor lesion but not in a distantly implanted TNFR1 KO tumor. Secondary mediators chiefly include CXCR1/2-acting chemokines, prostaglandin-E2 and TNFα itself. Knocking-down TNFR1 in a human tumor cell line rendered comparable results when xenografted. Analyses of scRNA-seq and spatial transcriptomics datasets from human solid tumors corroborate the role of TNFR1 on tumor cells in the induction of secondary pro-tumor inflammatory mediators.","dates":{"publication":"2026/08/12"},"accession":"GSE334550","cross_references":{"GSM":["GSM9790712","GSM9790713","GSM9790714","GSM9790715","GSM9790716","GSM9790717","GSM9790718"],"GPL":["28457"],"GSE":["334550"],"taxon":["Mus musculus"]}}