1. Dickkopf-1: A Promising Target for Cancer Immunotherapy
- Author
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Hang Yin Chu, Zihao Chen, Luyao Wang, Zong-Kang Zhang, Xinhuan Tan, Shuangshuang Liu, Bao-Ting Zhang, Aiping Lu, Yuanyuan Yu, and Ge Zhang
- Subjects
musculoskeletal diseases ,0301 basic medicine ,medicine.medical_treatment ,Immunology ,Cell ,Review ,Wnt signaling pathway ,Immunomodulation ,Structure-Activity Relationship ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cancer immunotherapy ,Neoplasms ,Biomarkers, Tumor ,medicine ,cancer ,Animals ,Humans ,Immunology and Allergy ,Molecular Targeted Therapy ,Immune Checkpoint Inhibitors ,beta Catenin ,DKK1 ,business.industry ,immune surveillance ,Disease Management ,Cancer ,Immunotherapy ,RC581-607 ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Intercellular Signaling Peptides and Proteins ,immunotherapy ,Disease Susceptibility ,Immunologic diseases. Allergy ,business ,CD8 ,Signal Transduction - Abstract
Clinical studies in a range of cancers have detected elevated levels of the Wnt antagonist Dickkopf-1 (DKK1) in the serum or tumors of patients, and this was frequently associated with a poor prognosis. Our analysis of DKK1 gene profile using data from TCGA also proves the high expression of DKK1 in 14 types of cancers. Numerous preclinical studies have demonstrated the cancer-promoting effects of DKK1 in both in vitro cell models and in vivo animal models. Furthermore, DKK1 showed the ability to modulate immune cell activities as well as the immunosuppressive cancer microenvironment. Expression level of DKK1 is positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) in 20 types of cancers, while negatively associated with CD8+ T cells in 4 of these 20 cancer types. Emerging experimental evidence indicates that DKK1 has been involved in T cell differentiation and induction of cancer evasion of immune surveillance by accumulating MDSCs. Consequently, DKK1 has become a promising target for cancer immunotherapy, and the mechanisms of DKK1 affecting cancers and immune cells have received great attention. This review introduces the rapidly growing body of literature revealing the cancer-promoting and immune regulatory activities of DKK1. In addition, this review also predicts that by understanding the interaction between different domains of DKK1 through computational modeling and functional studies, the underlying functional mechanism of DKK1 could be further elucidated, thus facilitating the development of anti-DKK1 drugs with more promising efficacy in cancer immunotherapy.
- Published
- 2021