{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334028/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334028"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"B7-H3 mediates immune escape and metastasis in SCLC through CXCL11/CXCR7/NFIB axis","description":"Small-cell lung cancer (SCLC) is an aggressive malignancy that is generally considered an immune desert. The therapeutic impact of immune checkpoint inhibitors in SCLC is modest and confined to a small population of patients. The immune checkpoint protein B7-H3 (also known as CD276) is highly expressed in SCLC; however, its functional contribution to SCLC remains unexplored. Here, to dissect tumor-intrinsic and immunomodulatory functions of B7-H3, we generated a novel genetically engineered mouse (GEM) model Rb1fl/fl; Trp53fl/fl; LSL-MycT58A; Cd276fl/fl (RPMC). Cd276 deletion significantly impaired primary tumor growth, metastatic dissemination, and reprogrammed the SCLC tumor microenvironment by increasing CD8+ T-cell infiltration and decreasing immunosuppressive myeloid populations. Loss of B7-H3 also improved responsiveness to combination therapy (cisplatin and anti-PD-L1) by modulating the anti-tumor immune response. Mechanistically, B7-H3 regulates NFIB through a CXCL11-CXCR7 feed-forward loop. To further evaluate translational implications, we tested a B7-H3 targeted antibody-drug conjugate m276-SL-PBD, which abrogated SCLC in the GEM model. Collectively, our findings establish B7-H3 as a key regulator of SCLC progression, metastatic competence, and immune escape, and highlight B7-H3-directed therapies as promising strategies for this recalcitrant disease.","dates":{"publication":"2026/10/01"},"accession":"GSE334028","cross_references":{"GSM":["GSM9779405","GSM9779406","GSM9779401","GSM9779402","GSM9779403","GSM9779404"],"GPL":["21697"],"GSE":["334028"],"taxon":["Homo sapiens"]}}