{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE238nnn/GSE238087/"]},"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=GSE238087"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Nanodrug modified with engineered cancer cell membrane targets CDKs to activate PD-L1 antibody immunotherapy against liver metastasis of immune-desert colon cancer","description":"Immunotherapy based on the PD-1/PD-L1 axis blockade has no benefit for patients diagnosed with colon cancer liver metastasis (CCLM) for the MSS/pMMR subtype, which is known as an immune-desert cancer featuring poor immunogenicity and insufficient CD8+ T cell infiltration in the tumor microenvironment. Thus, turning the tumor microenvironment immunologically hot is critical for activating a potent immunotherapy through immune checkpoint blockade (ICB) in this unique subtype accounting for 85% cases of total colon cancer. Here, a multifunctional nanodrug (NP-D@MP) carrying a cyclin-dependent kinase (CDK)1/2/5/9 inhibitor and PD-L1 antibody to boost the ICB-based immunotherapy against MSS/pMMR CCLM via reversing the immunosuppressive tumor microenvironment. To enhance the MSS/pMMR CCLM-targeting efficacy, we modified the nanodrug with PD-L1 knockout cell membrane of this colon cancer subtype. The nanodrug boosted the immunogenicity of tumor microenvironment, thus improving response rate of PD-L1 antibody treatment. First, CDK inhibitor (CDKi) delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells (TAMCs) sensitizing ICB therapy in CCLM of murine CT26 cell. Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft (PDX) model and the patient-derived organoid (PDO) model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the TIME, and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.","dates":{"publication":"2026/07/23"},"accession":"GSE238087","cross_references":{"GSM":["GSM7658360","GSM7658361","GSM7658364","GSM7658365","GSM7658362","GSM7658363","GSM7658357","GSM7658358","GSM7658366","GSM7658355","GSM7658356","GSM7658359"],"GPL":["17021"],"GSE":["238087"],"taxon":["Mus musculus"]}}