Immune response evasion is one of the hallmark features of cancer, which is not only the basis for cancer progression and metastasis but also affects the clinical management of cancer. Tumor immune evasion is mainly attributed to the dynamic and immunosuppressive tumor microenvironment (TME), which is regulated by a complex system including immunosuppressive cells and cytokines. Interleukin-18 (IL-18) is an important cytokine that plays a multifaceted role in immune system regulation, and its function is strictly regulated by the natural antagonist IL-18 binding protein (IL-18BP). IL-18 exhibits context-dependent immunoregulatory characteristics (acting as a “context resistor”) during tumor occurrence and progression, which is closely related to cancer type, stage, and the signaling network of the tumor microenvironment. The multifaceted functions of IL-18 have been utilized in cancer treatment to reduce the phenomenon of immune escape of tumors. With the latest advancements in cancer research related to IL-18, it is necessary to integrate the latest research findings to deepen the understanding of the mechanism of tumor immune escape and promote the improvement of cancer treatment levels. This review will systematically elaborate on the action mode, core regulatory mechanism and key signaling pathways of IL-18 in tumor immune evasion, analyze the heterogeneity patterns associated with its context-dependent effects, comprehensively sort out the core obstacles in clinical translation, and at the same time, envision new precision treatment strategies based on IL-18 regulation.

LncRNA H19 is a crucial regulatory player in GC and could operate as an attractive biomarker for patient prognosis. This meta-analysis aims to gauge the link between lncRNA H19 expression levels and patient prognosis, as well as clinicopathological features. HR and 95%CI were utilized to evaluate the connection between lncRNA H19 expression and prognosis, as well as clinicopathological features in GC patients. Bioinformatics analysis, potential molecular mechanisms and drug therapy involving lncRNA H19 were predicted through databases. The expression of lncRNA H19 in GC cells was verified through qRT-PCR. High expression of lncRNA H19 is correlated with a lower overall survival rate in GC patients, as well as TNM stage, lymph node metastasis and tumor invasion. Bioinformatics analysis confirmed that lncRNA H19 is significantly expressed in GC and related to poor prognosis. Function prediction analyses suggested that lncRNA H19 may contribute to GC progression through ceRNA regulatory networks, TFs, and predicted interactions with RBPs. Nutlin-3, PD-0332991, and Topotecan were predicted as preliminary candidate drugs. LncRNA H19 was confirmed to be highly expressed in GC cells. LncRNA H19 might act as a feasible biomarker for prognostic prediction in GC, warranting further validation in clinical studies.

Notably, certain ginsenoside components exhibit distinct bidirectional and context-dependent regulatory effects on ferroptosis depending on the disease setting. In aberrantly proliferating or activated cells, ginsenosides function as ferroptosis inducers, whereas in damaged quiescent cells of normal tissues, they act as ferroptosis inhibitors. The pro-ferroptotic effect is predominantly observed in cells characterized by abnormal proliferation or activation, such as cancer cells and activated hepatic stellate cells in liver fibrosis. In this context, ginsenosides modulate key iron metabolism proteins and suppress antioxidant defense systems (e.g., GPX4, SLC7A11), thereby triggering intracellular iron overload and explosive lipid peroxidation, ultimately culminating in ferroptosis. Conversely, the anti-ferroptotic effect primarily targets damaged non-proliferative cells in normal tissues subjected to pathological insults (e.g., ischemia–reperfusion, inflammation). In this setting, the regulatory focus of ginsenosides shifts toward maintaining iron homeostasis through mechanisms including upregulation of iron storage proteins (e.g., FTH1), downregulation of iron uptake proteins (e.g., TFRC), and inhibition of labile Fe²⁺ accumulation, thereby blocking ferroptosis initiation. This review systematically elucidates the pharmacological effects and underlying mechanisms by which different ginsenoside components regulate ferroptosis across various disease contexts and cell types, with particular emphasis on their disease- and cell type-dependent bidirectional regulatory characteristics. By highlighting these context-specific effects, we aim to provide novel potential therapeutic targets and mechanistic insights for the precision treatment of diverse pathological conditions, including malignant proliferative disorders, non-malignant aberrantly activated/proliferative diseases such as liver fibrosis, and cell injury/degenerative diseases.