What question did this study set out to answer?

The aim is to understand how the C118S mutation affects immune and metabolic changes in KRASG12D-driven pancreatic tumors in obese contexts.

April 5, 2026Cancer Research0 citations

Abstract 5565: C118S-mediated redox modulation of KRASG12D mutation reprograms immunometabolism to suppress obesity-driven pancreatic tumorigenesis

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ZRZahid RafiqThe University of Texas at El Paso WLWeiqin LuThe University of Texas at El Paso

Key Points

The aim is to understand how the C118S mutation affects immune and metabolic changes in KRASG12D-driven pancreatic tumors in obese contexts.
Utilized genetically engineered mouse models of KRASG12D/+ and KRASG12D+C118S/+
Monitored tumor progression under high-fat or normal diets
Conducted H&E, Alcian Blue, and Sirius Red staining for histological analysis
Performed immunohistochemistry for cell proliferation and immune marker expression
Measured ROS and KRAS activity alongside downstream signaling pathways.
C118S mutation slowed PDAC progression and reduced high-grade PanIN lesions
Lowered mucin production and fibrosis, indicating less aggressive tumor behavior
Decreased cell proliferation and altered ductal marker expression
Improved immune and metabolic profiles in tumor microenvironment under obesity
Reduced ROS activity led to suppression of oncogenic signaling.

Abstract

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is frequently driven by oncogenic KRASG12D/+ and exacerbated by obesity-induced metabolic inflammation, driving immune suppression and metabolic reprogramming. The concurrent rise in global obesity and PDAC incidence demands mechanistic strategies specifically tailored to the unique biology of obesity-associated KRAS-mutant tumors. Redox-sensitive regulation of KRAS at cysteine118 (C118) plays a critical role in signaling activity, and mutation to serine (C118S) has been shown to attenuate KRAS function in other tumor models. However, the impact of C118S on the immunometabolism landscape of KRASG12D/+ driven PDAC particularly in the context of obesity remains unexplored. This study aims to characterize how the C118S mutation alters immune and metabolic dynamics in obese versus lean PDAC settings. Methods Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5565.

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Abstract 5565: C118S-mediated redox modulation of KRASG12D mutation reprograms immunometabolism to suppress obesity-driven pancreatic tumorigenesis

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