A variety of cells, the most significant of which are cancer stem cells, make up malignant tumours. Through immune response evasion, these cells can grow new malignant tumours.
Finding cancer stem cell biomarkersand creating treatments that specifically target these cells have been the main goals of research.Regretfully, these efforts have not yet produced highly effective candidate medications in clinical trials.
A group of researchers at Hokkaido University’s Institute for Genetic Medicine, under the direction of Associate Professor Haruka Wada, looked into the ways in which cancer stem cells avoid the immune system in mouse models.
It was demonstrated that cancer stem cells cause macrophages, which are immune cells in charge of the initial stage of cancer cell death, to undergo senescence. The Journal for ImmunoTherapy of Cancer reported their findings.
“One of the biggest questions in the development of cancer is how cancer develops in individuals with a healthy immune system,” explains Wada.
“The majority of studies on cancer stem cells have been carried out in vitro or in immunodeficient mice models, which do not account for a fully functioning immune response. The lack of effectiveness of cancer stem cell-targeting drugs indicates that the immune response or lack thereof is more important than previously considered.”
The team used two cell lines of glioblastoma tumour, one of which was capable of inducing tumour formation (cancer stem cell) and the other of which was not.
In mice models, the cancer stem cells suppressed the proliferation of macrophages; further investigation showed that macrophages cultured with cancer stem cells exhibit senescence or cellular ageing.
Macrophages were not the only immune cells affected; while the proliferation of T cells was unchanged, their antitumor activity was suppressed due to the immunosuppressive factors produced by senescent macrophages.
The team identified interleukin 6 (IL-6) produced by cancer stem cells as the molecule responsible for triggering these effects.
The team also demonstrated that supplementing the mice inoculated with cancer stem cells with a molecule called nicotinamide mononucleotide resulted in the proliferation of non-senescent macrophages and reduced the immunosuppressive factors produced by senescent macrophages, preventing tumour growth and leading to increased survival times in mice.
“Our results indicate that drugs targeting senescent macrophages could be a treatment for cancer–an unprecedented development,” concluded Wada.
“We believe that these drugs could be part of a treatment that prevents the new onset of tumours, as well as a therapy that prevents recurrence after cancer treatment.”
Future work will focus on two avenues: confirming that this discovery holds true for cancers other than glioblastomas, and confirming that the findings apply to cancers in humans.