Nat Med: Key Factors Determining the Anticancer Effect of Immunological Checkpoint Therapy

Stimulatory dendritic cells (SDCs) play a key role in stimulating cytotoxic T lymphocytes and promoting immune responses against cancer. Studying the mechanisms that regulate the abundance of SDCs in the tumor microenvironment (TME) will provide new therapeutic strategies.

 

 

Rencently, researchers from the University of California, San Francisco, studied the abundance in human melanoma and the influencing factors of SDC, and found it was associated with intratumoral expression of the cytokine FLT3LG. The research related was recently published in Nature Medicine, entitled “A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments”.

 

FLT3LG is mainly secreted by lymphocytes in mouse and human tumors, especially natural killer (NK) cells. NK cells can form stable conjugates with SDCs in mouse TME. By using genetic means or drugs to remove NK cells from mice, the researchers found that NK cells play a key role in the positive regulation of SDCs in tumors by expressing FLT3L.

 

The researchers also found that although anti-PD-1 immunological checkpoint therapy primarily targets T cells, NK cells are often associated with protective SDCs in human tumors, patient response to PD-1 therapy, and prolonged overall patient survival.

 

Collectively, the study reveals that innate immune SDCs, the NK cell axis, can serve as a prognostic factor for predicting tumor-targeted T-cell tumor immunotherapy and that these innate immune cells are necessary to enhance T-cell response to tumors, so this pathway is a potential target for novel immunotherapies.

 

 

 

Reference

Kevin C. Barry et al, A natural killer-dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments, Nature Medicine (2018). DOI: 10.1038/s41591-018-0085-8