2. Academic Validation
  3. Tuft and Cancer Stem Cell Marker DCLK1: A New Target to Enhance Anti-Tumor Immunity in the Tumor Microenvironment

Tuft and Cancer Stem Cell Marker DCLK1: A New Target to Enhance Anti-Tumor Immunity in the Tumor Microenvironment

  • Cancers (Basel). 2020 Dec 17;12(12):3801. doi: 10.3390/cancers12123801.
Zhiyun Cao 1 2 3,  Nathaniel Weygant 1 2 3,  Parthasarathy Chandrakesan 4 5 6,  Courtney W Houchen 4 5 6,  Jun Peng 1 2 3,  Dongfeng Qu 4 5 6
Affiliations

Affiliations

  • 1 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
  • 2 Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
  • 3 Key Laboratory of Integrative Medicine of Fujian Province University, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
  • 4 Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • 5 Peggy and Charles Stephenson Cancer Center, Oklahoma City, OK 73104, USA.
  • 6 Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA.
PMID: 33348546 DOI: 10.3390/cancers12123801
Abstract

Microtubule-associated doublecortin-like kinase 1 (DCLK1) is an accepted marker of tuft cells (TCs) and several kinds of Cancer Stem Cells (CSCs), and emerging evidence suggests that DCLK1-positive TCs participate in the initiation and formation of inflammation-associated Cancer. DCLK1-expressing CSCs regulate multiple biological processes in Cancer, promote resistance to therapy, and are associated with metastasis. In solid tumor cancers, tumor epithelia, immune cells, cancer-associated fibroblasts, endothelial cells and blood vessels, extracellular matrix, and hypoxia all support a CSC phenotype characterized by drug resistance, recurrence, and metastasis. Recently, studies have shown that DCLK1-positive CSCs are associated with epithelial-mesenchymal transition, angiogenesis, and immune checkpoint. Emerging data concerning targeting DCLK1 with small molecular inhibitors, monoclonal antibodies, and chimeric antigen receptor T-cells shows promising effects on inhibiting tumor growth and regulating the tumor immune microenvironment. Overall, DCLK1 is reaching maturity as an anti-cancer target and therapies directed against it may have potential against CSCs directly, in remodeling the tumor microenvironment, and as immunotherapies.

Keywords

DCLK1; cancer stem cells; immunotherapies; microenvironment; tuft cells.

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