Dendritic cells (DCs) patrol the body and alert the adaptive immune system to pathogens or cancerous cells. They have traditionally been divided into two tribes, cDC1 and cDC2, based on molecular markers and their priming of distinct T cell responses. cDC1 cells appear to be uniform, have been well characterized and are known to provoke killer T cell responses. But cDC2 cells were less well understood. A study led by Ludwig MSK Director Alexander Rudensky and published in Cell in October just changed that. Alexander and his team profiled gene expression in thousands of individual cDC2 cells from mice and found that this DC tribe consists of two distinct clans, now named cDC2A and B. The former seems anti-inflammatory and primarily concerned with wound-healing; the latter tends to direct inflammatory T cell responses. Alexander and his team found that human cDC2 cells shared these same divisions. The findings suggest that the two cDC2 clans could play opposing roles in the development of cancer—cDC2A cells, for example, could be nurturing tumor growth, while cDC2B could be targeting cancer cells. In support of this possibility, the researchers found cDC2A cells hiding out in melanoma tumors taken from patients. The work opens a door to the design of new immunotherapies.
This article appeared in the April 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).