Cells with therapeutic potential have distinct subpopulations

Dendritic cells in skin

Dendritic cells (DCs) are important components of the immune system, where they take up antigens and present them to T cells. DCs stimulate T cells and cause their expansion such that they can track down and fight threats in the body, such as viruses or cancerous cells. DC-based vaccines have shown some promise treating prostate cancer and a number of clinical trials are ongoing for other cancer targets. DCs track down cancer cells, break them up into pieces (antigens), and display the antigens on their surfaces. T cells then “see” these antigens and track them down, destroying the cells that possess them.

DC vaccines are autologous therapies, meaning they use a patient’s own cells. These therapies are generated from blood drawn from the patient and the patient’s own tumor cells. In the laboratory, the DCs mature from peripheral blood mononuclear cells through exposure to specific growth factors and tumor antigens.

Many immuno-oncology therapies, such as chimeric antigen receptor T cell therapy (CAR-T) and T cell receptor (TCR) therapies, require DCs to stimulate T cells. Numerous clinical trials are ongoing for these promising therapies.

New insight into dendritic cell progenitors

An article recently published in the journal Science details how a dendritic cell develops from progenitor cells. An international team of researchers analyzed transcriptional regulation of single dendritic cells. This work demonstrated that rather than sharing a single progenitor cell, subtypes of DCs derive from different progenitors.

Human DCs are developed initially in the bone marrow and then differentiate further in the peripheral blood. Early in the process they identified distinct lineage-committed subpopulations which demonstrated functional differences. In order to study individual cells in such detail, the investigators employed elegant techniques such as single cell transcriptomics and cytometry by time-of-flight (TOF).

This research sheds new light on the DC development cycle and immune response regulations. Considering the importance of DCs in new therapies and vaccines for cancer, infectious disease and other indications, this work has potential to contribute to advances in next-generation therapeutic development.

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