Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.

Although immune checkpoint-based cancer immunotherapy has shown significant efficacy in various cancers, resistance still limits its therapeutic effects. Ubiquitination modification is a mechanism that adds different types of ubiquitin chains to proteins, mediating protein degradation or altering their function, thereby affecting cellular signal transduction. Increasing evidence suggests that ubiquitination modification plays a crucial role in regulating the mechanisms of resistance to cancer immunotherapy. Drugs targeting ubiquitination modification pathways have been shown to inhibit tumor progression or enhance the efficacy of cancer immunotherapy. This review elaborates on the mechanisms by which tumor cells, immune cells, and the tumor microenvironment mediate resistance to cancer immunotherapy and the details of how ubiquitination modification regulates these mechanisms, providing a foundation for enhancing the efficacy of cancer immunotherapy by intervening in ubiquitination modification.