GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334550/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334550GEOGSEfalseTNFR1 expression on cancer cells is critical for immune escape shaping an immunosuppressive tumor microenvironmentTNFα 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.2026/08/12GSE334550GSM9790712GSM9790713GSM9790714GSM9790715GSM9790716GSM9790717GSM979071828457334550Mus musculus