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Dickkopf-1: A Promising Target for Cancer Immunotherapy
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 12 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
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.
- 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
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....0be050e9c51c9d291c3bb3d76b5e19b3