Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming

作者：Lin Tian, Hui Li, Heran Cui, Chenchen Tang, Peiyan Zhao, Xinyue Wang, Ying Cheng · 发表于：Cell Death and Disease · 年份：2025 · DOI：10.1038/s41419-025-08101-1 · 被引用次数：23 · 研究领域：Protein Kinase Regulation and GTPase Signaling、Cancer Research and Treatments、PI3K/AKT/mTOR signaling in cancer

The KRAS mutation represents the most prevalent oncogenic alteration observed in human cancers. Its primary role involves directly driving malignant tumor development and growth through the activation of downstream signaling pathways. Increasing evidence suggests that KRAS significantly affects the immune response of KRAS-mutant tumors by modulating immune-related signaling and inflammatory pathways. In addition to broadly regulating the KRAS-associated immune signaling, KRAS influences immune cell phenotype and function by triggering tumor metabolic pathways. Here, we reviewed the KRAS mutation-associated immune microenvironment features and discussed how KRAS remodels the immune microenvironment by regulating immune-related molecules, inflammatory factors, and multiple metabolic pathways, offering insights that could be useful for developing effective immune-responsive therapies for KRAS-mutant tumors.