The role of protein SUMOylation in cancer immunotherapy and its therapeutic strategies

SUMOylation is a post-translational protein modification in which SUMO molecules are covalently attached to substrate proteins via the concerted action of activating enzymes, conjugating enzymes and ligases, followed by de-SUMOylation mediated by de-SUMOylating enzymes to form a dynamic regulatory cycle. It participates extensively in critical biological processes including cell proliferation, differentiation, DNA damage repair, and the regulation of gene expression. Accumulating studies have demonstrated that dysregulation of SUMOylation contributes substantially to the initiation and progression of multiple malignant tumors. Aberrant SUMOylation can affect the malignant phenotype and clinical progression of tumor cells by regulating the activation of oncogenes, the inactivation of tumor suppressor genes, the remodeling of the tumor microenvironment, and immune escape-related pathways. This article systematically reviews the molecular mechanisms and biological functions of SUMOylation, with a focus on its core role in regulating tumor immune responses and mediating tumor immune escape. It summarizes various strategies and research progress for enhancing the efficacy of tumor immunotherapy by targeting the SUMO pathway, and discusses future research directions and clinical translation prospects in this field. These findings provide a theoretical basis for a deeper understanding of tumor pathogenesis and the development of novel anti-tumor treatment strategies.