FMS-like tyrosine kinase 3 ligand

FMS-like tyrosine kinase 3 ligand (FLT3L) is an endogenous small molecule that functions as a cytokine and growth factor that increases the number of immune cells (lymphocytes (B cells and T cells)) by activating the hematopoietic progenitors. It acts by binding to and activating FLT3 (CD135) which is found on what (in mice) are called multipotent progenitor (MPP) and common lymphoid progenitor (CLP) cells. It also induces the mobilization of the hematopoietic progenitors and stem cells in vivo which may help the system to kill cancer cells.[1]

FLT3L is crucial for steady-state plasmacytoid dendritic cell (pDC) and classical dendritic cell (cDC) development.[1][2] A lack of FLT3L results in low levels of dendritic cells.

FLT3L in parasite clearance

FLT3L and its receptor are involved in the mammalian immune response to malaria. In strains of plasmodium, FLT3L was shown to be released from mast cells and cause the expansion of dendritic cells, leading to the activation of CD8+ T cells. The same paper suggested that FLT3L release was caused by stimulation of mast cells with uric acid, produced from a precursor secreted by the plasmodium parasite. .[3]

FLT3L in immunotherapy

In situ vaccine (ISV), combining Flt3L, local radiotherapy, and a TLR3 agonist (poly-ICLC), could recruit, antigen-load and activate intratumoral cross-presenting dendritic cells (DCs) in indolent non-Hodgkin’s lymphomas (iNHLs) treatment (clinical trial: NCT01976585).[4] In this study, intratumoral Flt3L was able to (1) induce the accumulation of large numbers of TLR3+ DCs in the tumor and (2) mediate , together with local irradiation, cross-presentation of TAA by DCs in vitro and in vivo.


References
  1. Shortman, Ken; Naik, Shalin H. (2006). "Steady-state and inflammatory dendritic-cell development". Nature Reviews Immunology. 7 (1): 19–30. doi:10.1038/nri1996. PMID 17170756.
  2. Rahman, Adeeb H.; Aloman, Costica (2013). "Dendritic cells and liver fibrosis". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1832 (7): 998–1004. doi:10.1016/j.bbadis.2013.01.005. PMC 3641166. PMID 23313573.
  3. Guermonprez, Pierre; Helft, Julie (2013). "Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection". Nature Medicine. 19 (1): 730–738. doi:10.1038/nm.3197. PMC 3914008. PMID 23685841.
  4. Hammerich, Linda; Marron, Thomas U.; Upadhyay, Ranjan; Svensson-Arvelund, Judit; Dhainaut, Maxime; Hussein, Shafinaz; Zhan, Yougen; Ostrowski, Dana; Yellin, Michael; Marsh, Henry; Salazar, Andres M.; Rahman, Adeeb H.; Brown, Brian D.; Merad, Miriam; Brody, Joshua D. (8 April 2019). "Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination". Nature Medicine. p. 1. doi:10.1038/s41591-019-0410-x.

Further reading


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