Intricate confrontation: Research progress and application potential of TRIM family proteins in tumor immune escape

Tripartite motif (TRIM) family proteins have more than 80 members and are widely found in various eukaryotic cells. Most TRIM family proteins participate in the ubiquitin-proteasome degradation system as E3-ubiquitin ligases; therefore, they play pivotal regulatory roles in the occurrence and development of tumors, including tumor immune escape. Due to the diversity of functional domains of TRIM family proteins, they can extensively participate in multiple signaling pathways of tumor immune escape through different substrates. In current research and clinical contexts, immune escape has become an urgent problem. The extensive participation of TRIM family proteins in curing tumors or preventing postoperative recurrence and metastasis makes them promising targets.

The aim of the review is to make up for the gap in the current research on TRIM family proteins and tumor immune escape and propose future development directions according to the current progress and problems.

This up-to-date review summarizes the characteristics and biological functions of TRIM family proteins, discusses the mechanisms of TRIM family proteins involved in tumor immune escape, and highlights the specific mechanism from the level of structure-function-molecule-pathway-phenotype, including mechanisms at the level of protein domains and functions, at the level of molecules and signaling pathways, and at the level of cells and microenvironments. We also discuss the application potential of TRIM family proteins in tumor immunotherapy, such as possible treatment strategies for combination targeting TRIM family protein drugs and checkpoint inhibitors for improving cancer treatment.