Dickkopf-1: A Promising Target for Cancer Immunotherapy

Hang Yin Chu, Zihao Chen, Luyao Wang, Zong-Kang Zhang, Xinhuan Tan, Shuangshuang Liu, Bao-Ting Zhang, Aiping Lu, Yuanyuan Yu*, Ge Zhang*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Article number658097
Number of pages14
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 20 May 2021

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • cancer
  • DKK1
  • immune surveillance
  • immunotherapy
  • Wnt signaling pathway

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