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Regulation of Cancer Immune Checkpoint: Mono- and Poly-Ubiquitination: Tags for Fate

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Regulation of Cancer Immune Checkpoints

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1248))

Abstract

The antagonism, stalemate and compromise between the immune system and tumor cells is closely associated with tumor development and progression. In recent years, tumor immunotherapy has made continuous breakthroughs. It has become an important approach for cancer treatment, improving the survival and prognosis of more and more tumor patients. Further investigating the mechanism of tumor immune regulation, and exploring tumor immunotherapy targets with high specificity and wide applicability will provide researchers and clinicians with favorable weapons towards cancer. Ubiquitination affects protein fate through influencing the activity, stability and location of target protein. The regulation of substrate protein fate by ubiquitination is involved in cell cycle, apoptosis, transcriptional regulation, DNA repair, immune response, protein degradation and quality control. E3 ubiquitin ligase selectively recruits specific protein substrates through specific protein-protein interactions to determine the specificity of the overall ubiquitin modification reaction. Immune-checkpoint inhibitory pathway is an important mechanism for tumor cells to evade immune killing, which can inhibit T cell activity. Blocking the immune checkpoints and activating T cells through targeting the negative regulatory factors of T cell activation and removing the “brake” of T lymphocytes can enhance T cells immune response against tumors. Therefore, blocking the immune checkpoint is one of the methods to enhance the activity of T cells, and it is also a hot target for the development of anti-tumor drugs in recent years, whose inhibitors have shown good effect in specific tumor treatment. Ubiquitination, as one of the most important posttranslational modification of proteins, also modulates the expression, intracellular trafficking, subcellular and membranous location of immune checkpoints, regulating the immune surveillance of T cells to tumors.

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  1. Renji Hospital, Shanghai Jiao Tong University, Shanghai, 200001, China

    Han Yao

  2. Institutes of Biomedical Sciences, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200032, China

    Jie Xu

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    Jie Xu

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Yao, H., Xu, J. (2020). Regulation of Cancer Immune Checkpoint: Mono- and Poly-Ubiquitination: Tags for Fate. In: Xu, J. (eds) Regulation of Cancer Immune Checkpoints. Advances in Experimental Medicine and Biology, vol 1248. Springer, Singapore. https://doi.org/10.1007/978-981-15-3266-5_13

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