Harnessing dendritic cells to treat cancer and inflammatory diseases

Dendritic cells (DCs) are uniquely equipped to prime T cell responses against foreign antigens and induce and maintain Tregs against self-antigens, making them a great target for the treatment of cancer and inflammatory diseases. This is because they have a unique machinery to sense damage, to capture and process cell associated antigens and very importantly to migrate charged with antigen cargo to the T zones of the tissue-draining lymph nodes to instruct T cell differentiation programs.

Recently, the use of single cell profiling of human and mice tissues revealed a DC molecular state expressing within the same DC both mature immunogenic and regulatory molecules as well as a migratory program that promote DC migration to lymphoid structures we named “mregDC” [Maier et al. 2020]. We found that the mregDC state is triggered in tissue resident DC upon capture of cell-associated antigens and the identification of this program helps define the antigen charged DC that are interacting with T cells. A big focus of the lab is to use functional genomic screens developed by the Brown lab to learn how to uncouple regulatory from immunogenic programs in mregDC in cancer and inflammatory diseases.

Key references

1. Ginhoux et al. JEM 2009
2. Bogounovic et al. Immunity 2009
3. Miller et al. Nature Immunology 2012
4. Helft et al. JCI 2012
5. Merad et al. ARI 2013
6. Salmon et al. Immunity 2016
7. Maier et al. Nature 2020