Dendritic cell Flt3 - regulation, roles and repercussions for immunotherapy
- PMID: 34097779
- DOI: 10.1111/imcb.12484
Dendritic cell Flt3 - regulation, roles and repercussions for immunotherapy
Abstract
Dendritic cells (DCs) are essential for initiating immune responses. Depending on the environment, the type of DC and the way in which they interact with T cells, these immune responses can be beneficial or detrimental. DCs can be exploited as cellular vectors for vaccines against infection and cancer. The development and maintenance of DCs is dependent on the FMS-like tyrosine kinase 3 (Flt3)/Flt3 ligand (Flt3L) signaling cascade. Flt3 is also one of the most commonly mutated genes in acute myeloid leukemia and as such represents an attractive drug target. In this review, Flt3 is discussed with a particular focus on DCs. We detail the lifecycle of Flt3, from transcription to degradation, and interrogate recent studies as to how this pathway can be manipulated for immunotherapy, vaccination and treatment of autoimmune disease.
Keywords: Flt3; dendritic cells; immunity.
© 2021 Australian and New Zealand Society for Immunology, Inc.
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References
REFERENCES
-
- Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol 2020; 20: 7-24.
-
- Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973; 137: 1142-1162.
-
- Reis e Sousa C. Dendritic cells in a mature age. Nat Rev Immunol. 2006; 6: 476-483. http://dx.doi.org/10.1038/nri1845.
-
- Miller JC, Brown BD, Shay T, et al. Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol 2012; 13: 888-899.
-
- Hannum C, Culpepper J, Campbell D, et al. Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs. Nature 1994; 368: 643-648.
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