# IL-18-Mediated Tumor Immune Evasion

## TL;DR

This paper reviews how IL-18 influences tumor immune evasion and explores its role in cancer progression and treatment strategies.

## Contribution

The paper systematically reviews the context-dependent roles of IL-18 in tumor immune evasion and proposes new precision treatment strategies.

## Key findings

- IL-18 acts as a context resistor in tumor progression, influenced by cancer type and tumor microenvironment.
- Regulation of IL-18 offers potential for reducing tumor immune escape in cancer treatment.
- Heterogeneity patterns of IL-18 effects highlight challenges in clinical translation.

## Abstract

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.