By Matthew Lee ‘21
Scientists and students alike are often well aware that one of the immune system’s most important roles is fighting cancer. In this effort, dendritic cells are especially important; particularly important are conventional type 1 dendritic cells (cDC1). Dendritic cells are a type of immune cell. cDCs can present tumor antigens to T cells and attract T cells via the secretion of cytokines. Dr. Jan Böttcher of The Francis Crick Institute and a team of researchers further elucidated how the antitumor effectiveness of cDC1 is affected by natural killer (NK) cells and a type of prostaglandin, PGE2. Prostaglandins are common chemical messengers in the body that can affect receptors inside cells.
The researchers used PGE2 producing cells (COX) as control while cells engineered to be COX-were used as the experimental group. Compared to the controls, COX-deficient cells in mice tumors saw a significant increase in cDC1 accumulation and penetration. Accumulation was measured by quanityt of cDC1s present. Penetration was evident as cDC1s were farther away from the tumor perimeter and the outer edge of the tumor. Further experimentation revealed that NK cells were key to cDC1 proliferation and that the NK were found in multicell clusters distributed similarly to cDC1s.
NK cells produce several cytokines, but the two most important ones are XCL1 and CCL5. Compared to COX-sufficient tumors, COX-deficient tumors showed an at least 12 fold increase in CCL5 concentration and XCL1 mRNA expression. This indicates that PGE2 likely directly inhibits NK cells. The inhibitory effects of PGE2 go beyond NK cells, however. PGE2 also inhibits the ability of cDC1s to migrate towards XCL1 or CCL5 by reducing the number of cytokine receptors on cDC1 surface.
This study explored key players that regulate the propagation of cDC1 cells. Other factors to consider are the effects of substances other than PGE2 that may interact to regulate NK cells activity, and the mechanisms influencing cDC1 propagation in the presence of PGE2. The scientific community still has much to learn, but progress in this emerging field can one day be translated into potential cancer therapies
- J. Böttcher, et. al., NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control. Cell 172, 1-16 (2018). doi: 10.1016/j.cell.2018.01.004
- Image retrieved from: https://upload.wikimedia.org/wikipedia/en/d/d8/FDC_scanning_EM.jpg