Within the immune system, deadly predators called natural killer cells patrol the body and identify cancer and infected cells for destruction. However, when they are in the vicinity of lymphoma tumors, they lose their killer instinct. Thus, much-needed new therapies for lymphoma may come from finding ways to restore their power.
These were the findings of a study from the Helmholtz Zentrum München, in Germany, published in the European Journal of Immunology.
Natural killer cells – NK cells – are white blood cells of the innate immune system. They are vital soldiers in the body’s natural ability to fight against viral infection and cancer.
NK cells go around looking for virus-infected and cancer cells and mark them for destruction. They also send out signals that can trigger further immune responses against the targets.
Lymphomas are cancers of the lymphatic system. They arise in B cells or T cells and form at lymph nodes. B cell lymphomas are notoriously hard to treat, and new approaches to therapy are desperately needed, says the team behind the new study.
Previous research has suggested that NK cells have the potential to attack B lymphoma cells and should be investigated further as a possible avenue for new treatments.
But, others have also discovered that in living bodies as opposed to cells cultures, NK cells seem to lose their ability to tackle lymphoma tumor cells – so is there any use in pursuing this avenue?
In their new study, Ralph Mocikat, a professor of molecular immunology, and colleagues set out to explore this question. They ran one experiment that showed when placed in the vicinity of lymphoma tumors in live mice, NK cells lose their ability to kill the cancer cells.
And then they ran another experiment that showed when those same NK cells are put in a different environment, their ability to kill rogue cells comes back within a few hours.
These two experiments confirmed that it was the lymphoma that was somehow inactivating the NK cells, note the researchers.
In further tests, the team established the tumor uses two mechanisms to disable the NK cells. One mechanism involves a specific inflammatory molecule – a cytokine called IL-10 – that indirectly deactivates the NK cell.
The other mechanism lymphoma cells use to evade death by NK cells is they deactivate their NKG2D ligands. These ligands are surface molecules that allow the NK cells to attach to their victims and unleash their killer toxins.
However, despite these protective strategies from the tumor, the researchers note that the NK cells are still – at an early stage – able to send signals to activate further anti-tumor immune responses by producing a cytokine called interferon-gamma (IFN-γ).
The researchers conclude that it may still be possible to use NK cells to fight B cell lymphoma by priming them against the tumor before transplanting them to its vicinity – thus by-passing the steps the tumor takes to evade them.
A shot of IFN-γ or antibodies against IL-10 could boost the anti-tumor immune system response from other areas too, as Prof. Mocikat explains:
“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.”
Meanwhile, Medical News Today recently reported that researchers are suggesting doctors consider 2 years as a more practical survival goal for patients with a type of non-Hodgkin lymphoma called follicular lymphoma.
In the Journal of Clinical Oncology, a team led by an oncologist at the University of Rochester, explains that while most follicular lymphoma patients can expect to live 20 years, there is a distinct group of around 20% of patients that consistently experiences relapse within 2 years of receiving even the most up-to-date treatment.