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Review
. 2022 Nov 1:13:1065029.
doi: 10.3389/fphar.2022.1065029. eCollection 2022.

Deciphering the role of DOCK8 in tumorigenesis by regulating immunity and the application of nanotechnology in DOCK8 deficiency therapy

Longhui Zhang  1   2 , Yang Cao  3 , Xiangpeng Dai  1   2 , Xiaoling Zhang  1   2
Affiliations
Review

Deciphering the role of DOCK8 in tumorigenesis by regulating immunity and the application of nanotechnology in DOCK8 deficiency therapy

Longhui Zhang et al. Front Pharmacol. .

Abstract

The dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome is a severe immune disorder and characterized by serum IgE levels elevation, fungal and viral infections, dermatitis and food allergies. It was well known that DOCK8 is crucial for the survival and function of multiple immune related cells. However, the critical role of DOCK8 on tumorigenesis through regulating immunity is poorly investigated. Accumulating evidences indicated that DOCK8 could affect tumorigenesis by regulating the immunity through immune cells, including NK cells, T cells, B cells and dendritic cells. Here, we summarized and discussed the critical role of DOCK8 in cytoskeleton reconstruction, CD4+ T cell differentiation, immune synaptic formation, tumor immune infiltration, tumor immune surveillance and tumorigenesis. Furthermore, the potential roles of nanotechnology in improving the hematopoietic stem cell transplantation-based therapy for DOCK8 deficiency diseases are also highlighted and discussed.

Keywords: Cdc42; NK cells; cytoskeleton; dedicator of cytokinesis 8; hematopoietic stem cell transplantation; immunity; nanotechnology; tumor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The critical function of DOCK8 on the regulation of immunity. DOCK8 plays important role in regulating the immunity and maintaining the basic function of multiple immune cells. The main function of DOCK8 related to immunity included but not limited to the regulation of immune synapse, tumor immune infiltration, immune surveillance, cytoskeleton, and Th17 differentiation of CD4+ T cells.
FIGURE 2
FIGURE 2
DOCK8 deficiency was associated with tumorigenesis. DOCK8 deficiency might be an important inducer for multiple cancers initiation such as lung cancer, leukemia, lymphomatoid granulomatosis (LYG), hepatocellular carcinoma (HCC), neuroblastoma (NB) and others.
FIGURE 3
FIGURE 3
Potential applications of nanotechnology in HSCT in treating DOCK8 deficiency diseases. Nanotechnology could be used to produce the in vitro culturing platforms to expand the HSC with high efficiency, the drug delivery and release system to precisely deliver the immunosuppressants to desired therapeutic area and to achieve constant release of drugs, respectively.
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