TRIM family proteins: dual roles in tumor immunity

Tripartite motif (TRIM) proteins represent one of the largest subfamilies of E3 ubiquitin ligases and exert complex yet critical dual roles in tumor immunology by orchestrating protein ubiquitination. This review systematically delineates the multifaceted regulatory roles of TRIM proteins in tumor immunity, with a focus on their dual functions within the tumor immune microenvironment, particularly regarding immune checkpoints and tumor-infiltrating immune cells. Notably, the same TRIM protein may exert opposing immunomodulatory effects in different tumor types or microenvironmental contexts, underscoring the critical influence of context on their functions. This article aims to synthesize current advances in understanding the dual roles of the TRIM family in tumor immunity and to discuss their potential and challenges as novel targets for immunotherapy.