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IBI351, a novel KRASG12C inhibitor, enhances αPD-1 efficacy in KRASG12C mutant lung cancer

GSE328294 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/06/05 Platform GPL24676
Summary
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.
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Also filed as BioProject PRJNA1454496 and SRA study SRP692494. Searching any of these in the dataset finder brings you back here.

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