{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328294/"]},"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=GSE328294"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"IBI351, a novel KRASG12C inhibitor, enhances αPD-1 efficacy in KRASG12C mutant lung cancer","description":"The clinical benefit of immune checkpoint inhibitor (ICI) treatments in patients with advanced KRAS mutant non-small-cell lung cancer (NSCLC) is limited. Here, we found IBI351, a selective KRASG12C inhibitor, significantly enhanced the efficacy of anti-PD-1 antibody (αPD-1) in inhibiting tumor growth in vitro and in vivo. Mechanistically, IBI351 inhibited STAT3 activity, leading to downregulation of stanniocalcin 1 (STC1). STC1 anchors calreticulin (CRT) to the mitochondrial membrane; its downregulation promoted CRT translocation to the cancer cell surface, increasing the ‘eat me’ signal and enhancing T cell infiltration. In clinical specimens from KRASG12C mutant NSCLC patients treated with PD-1 inhibitors, low STC1 expression correlated with better treatment response and prolonged survival. Together, these findings demonstrate that IBI351 enhances ICI efficacy by suppressing the STAT3-STC1 axis and promoting CRT-mediated phagocytosis, supporting further clinical evaluation of this combination.","dates":{"publication":"2026/06/05"},"accession":"GSE328294","cross_references":{"GSM":["GSM9678027","GSM9678028","GSM9678026","GSM9678029","GSM9678030","GSM9678031"],"GPL":["24676"],"GSE":["328294"],"taxon":["Homo sapiens"]}}