{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE233nnn/GSE233462/"]},"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=GSE233462"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Ubiquitin D drives colorectal cancer immune evasion and resistance to anti PD1 immunotherapy","description":"Ubiquitin D drives colorectal cancer immune evasion and resistance to anti PD1 immunotherapy by suppressing FBXW7 mediaUbiquitin D drives colorectal cancer immune evasion and resistance to anti PD1 immunotherapy by suppressing FBXW7 mediated CD73 degradation [scRNA-seq] The majority of patients with colorectal cancer (CRC) can’t benefit from anti-PD-1 immunotherapy due to an insufficient T cell response in the tumor microenvironment (TME); however, the underlying mechanism remains unknown. Here, we show that ubiquitin D (UBD) in tumor cells inhibits CD8+ T cell‑mediated anti‑tumor responses, and consequently mediates resistance to anti‑PD‑1 immunotherapy in experimental and clinical CRC. Mechanistically, UBD disrupted E3 ligase F‑box and WD repeat domain‑containing 7 (FBXW7)‑induced proteasome degradation of CD73, thereby increasing the concentration of intracellular adenosine, which subsequently suppressed CD8+ T cell function in the TME. Importantly, blockade of CD73 sensitized UBD‑overexpressed cancer cells to anti-PD‑1 immunotherapy by restoring intratumor CD8+ T cell function. We have thus revealed a previously unrecognized mechanism for CRC resistance to anti‑PD‑1 therapy through UBD‑CD73‑adenosine mediated suppression of CD8+ T cells. This new information potentially provides a novel strategy to overcome resistance to PD‑1 blockade in patients with CRC.","dates":{"publication":"2026/05/23"},"accession":"GSE233462","cross_references":{"GSM":["GSM7428956","GSM7428955"],"GPL":["24247"],"GSE":["233462"],"taxon":["Mus musculus"]}}