In a new study entitled “Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma” a team of researchers at the Helmholtz Zentrum München, Germany discovered a potential mechanism that allows lymphomas to evade the activity of NK cells, key players of our immune system. The study was published in the European Journal of Immunology.
Lymphoma is a type of cancer that affects the lymphatic system, specifically arising in B cells or T cells. Natural killer cells (NK cells) are key players of the immune system, contributing to control infectious diseases and potentially tumor cells, since the immune system is also capable of mounting immune responses against cancer cells, such as it does against pathogens. However, what anti-tumoral function do NK cells exert against lymphomas is currently not well defined.
Here, researchers at the Helmholtz Zentrum München led by Prof. Dr. Ralph Mocikat of the Institute of Molecular Immunology (IMI), Helmholtz Zentrum München discovered, as previously suggested, that NK cells are capable of eliminating tumor cells in vivo. However, when sitting within the tumor microenvironment, NK cells lose their cytotoxic effect, which was almost immediately abrogated (in a few hours) if NK cells were placed in a normal, non-tumorigenic environment. These results suggest that tumor-releasing factors are imparing NK cellular functions.
The team performed further studies and identified two tumor-specific factors responsible for NK cells’ activity impairment – the inflammatory cytokine IL-10 and down-regulation of NK cells-binding factors, particularly NKG2D ligands – rendering NK cells incapable of completing their cytotoxic activity against tumors.
Their findings carry potential new therapeutic applications, as Dr. Mocikat noted, “Our results show that the transfer of NK cells is a possible strategic option to treat B cell lymphoma. According to our findings, this therapeutic approach can be optimized when transferred NK cells are already activated in vitro prior to their injection, thus bypassing the missing activation potential in the tumor microenvironment. An additional injection of IFN-γ or of antibodies against IL-10 could further support the immune activity.”
Future therapeutics targeting such factors can re-establish the active role of NK cells in the fight against lymphomas.