GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328294/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328294GEOGSEfalseIBI351, a novel KRASG12C inhibitor, enhances αPD-1 efficacy in KRASG12C mutant lung cancerThe 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.2026/06/05GSE328294GSM9678027GSM9678028GSM9678026GSM9678029GSM9678030GSM967803124676328294Homo sapiens