2023-11-14 15:46:56
Tumors are made up of a mixture of cells; Of all of them, the most important are cancer stem cells. These cells are capable of making new tumors by evading the immune response. Research so far has focused on identifying biomarkers of cancer stem cells and developing therapies targeting these cells. Unfortunately, the drug candidates developed from these efforts have so far not been very effective in clinical trials.
Now, a team of researchers led by Haruka Wada of the Hokkaido University Institute of Genetic Medicine (Japan) has examined the mechanisms by which cancer stem cells evade the immune response in mouse models.
In a study ‘Journal for ImmunoTherapy of Cancer‘Researchers demonstrate that cancer stem cells induce senescence in macrophages, the immune cells responsible for the first step of cancer cell destruction.
“One of the most important questions in cancer development is how the tumor develops in people with a healthy immune system,” explains Wada. ‘Most studies on cancer stem cells have been carried out in vitro or in immunodeficient mouse models, which do not represent a fully functioning immune response. Lack of effectiveness of drugs targeting cancer stem cells indicates that immune response or lack thereof is more important than previously thought ».
The team used two glioblastoma tumor cell lines, one of which was capable of inducing tumor formation (cancer stem cells) and the other was not.
In mouse models, cancer stem cells suppressed macrophage proliferation; Additional research demonstrated that macrophages cultured with cancer stem cells exhibit cellular senescence or aging.
Macrophages were not the only immune cells affected; Although T cell proliferation remained unchanged, their antitumor activity was suppressed due to immunosuppressive factors produced by senescent macrophages.
The team identified the interleukin 6 (IL-6) produced by cancer stem cells as the molecule responsible for triggering these effects.
The team also showed that supplementing mice inoculated with cancer stem cells with a molecule called nicotinamide mononucleotide resulted in the proliferation of non-senescent macrophages and reduced immunosuppressive factors produced by senescent macrophages, preventing tumor growth and increasing survival times. survival in mice.
Unprecedented progress
“Our results indicate that drugs targeting senescent macrophages could be a treatment for cancer, an unprecedented advance,” concludes Wada. “We believe that these medicines “They could be part of a treatment that prevents the new appearance of tumors, as well as a therapy that prevents recurrence after cancer treatment.”
Future work will focus on two avenues: confirming that this discovery is valid for cancers other than glioblastomas and confirming that the findings apply to human cancers.
#Cancer #cells #age #immune #system #form #tumors