Science Sub-journal: Reprogramming macrophages with CSF-1R inhibitors enhances the effectiveness of radiotherapy treatments for glioblastoma.

!--:pagetitle"--2 ---3(2020) -- In a new study, researchers from the Ludwig Institute of Cancer in Switzerland and the University of Lausanne analyzed how radiotherapy alters the behavior of macrophages (an immune cell) found in glioblastoma (GBM) and showed how these cells may be reprogrammed with existing drugs to suppress the ongoing recurrence of this aggressive brain cancer.
related findings were published on July 15, 2020 in the journal Science Translational Medicine, with the title "Dynamic changes in glioma populationages populationages s quetherapy reveal CSF-1R inhibition as a strategy to overcome the resistance".
the authors of the paper are Dr Johanna Joyce and Dr. Leila Akkari of the Ludwig Cancer Institute.
images from Science Translational Medicine, 2020, doi: 10.1126/scitranslmed.aaw7843.
study details how radiotherapy dynamically alters gene expression procedures in two subtypes of tumor-related macrophages (TAs) and describes how these changes push TAM into a state that helps treat resistance to the appearance and growth of tumors.
Joyce and her colleagues also demonstrated that combining radiotherapy with a daily drug that targets macrophages --- a set-stimulating factor-1 receptor (CSF-1R) inhibitor -- can reverse this transition and significantly extend the life of the GBM mouse model. "These preclinical data tell us that for GBM patients receiving radiation, adding CSF-1R inhibitors to treatment options may have an effect on extending survival,"
Joyce said.
"GBM patients usually live no longer than a year after diagnosis because the cancer inevitably recurs and is often resistant to multiple treatments."
it is not known --- TAM --- whether they are linked to cancer cell survival and resistance in a variety of tumor types--- will promote GBM resistance to ionizing radiation, which is part of the standard treatment for invasive tumors.
two types of macrophages are present in gliomas.
a type of macrophage is the brain's resident macrophages, or microglias.
another type of mononucleocellular-derived macrophage (monocyte-derived macrophage, MDM), which patrols the body, devours pathogens and dead cells or their residues, and initiates additional immune responses.
however, macrophages can be pushed into another state, often referred to as M2-like activated phenotype, in which they help the tissue heal rather than respond to threats.
many cancers induce macrophages into this surrogate type, which supports tumor survival and growth.
Joyce and her team found that both small glial cells and MDM flooded into the GBM tumors in mice to clean up the cell residue after the initial radiotherapy process.
but interestingly, when this neuroglioma recurs, MDM is dominated in the TAM population.
however, the gene expression spectrum in neurogliomas treated by chemotherapy is closer to that of small glial cells.
in addition, they found that MDM and small glial cells in gliomas treated by chemotherapy alternately alternating into wound healing phenotypes and secreting factors that promote DNA repair in the cells. "Not only have these macrophages change, but more importantly, they can now interfere with the efficacy of radiotherapy because they help cancer cells repair the DNA damage they cause,"
Joyce explains.
so you have this yin and yang double-day situation.
radiotherapy certainly destroyed many cancer cells, but it also caused all these macrophages to rush into the tumor to clean up the debris, and as a result they were super-activated, creating a tolerant environment for the remaining cancer cells to allow new tumors to form. "To see if specific removal of MDM can reverse this effect, the researchers used an antibody that blocks MDM into the brain to treat different GBM mouse models,"
.
, however, this is only a nominal improvement in the survival rate of one of the mouse models.
Joyce's lab has previously reported that CSF-1R inhibitors allow THE TAM to stay away from wound healing phenotypes, so they went on to test whether the strategy might enhance the efficacy of radiation therapy.
they found that 12 days of CSF-1R inhibitor therapy after radiotherapy enhanced the initial therapeutic response and extended the median survival of mice by about 3 weeks, compared to radiation alone.
, by contrast, the treatment of CSF-1R inhibition on a daily basis for several months after radiotherapy produced the most striking result: reprogramming tam and significantly extending median survival. "In this six-month study, we kept about 95 percent of the mice alive,"
Joyce said.
", the survival rate of mice transplanted with tumors from the patient's source increased.
Joyce and his colleagues are further exploring TAM mechanisms that promote DNA repair and otherways that help cancer cells survive in GBM.
(bioon.com) References: 1.Leila Akkari et al. Dynamics in glioma macrophage population s radio aftertherapy reveal CSF-1R inhibition as a strategy to the ford. Science Translational Medicine, 2020, doi: 10.1126/scitranslmed.aw7843.2. Reprogramming of the immune cells of the fields of the effects of the radiothein in preclinical models of brain cancer title "" - !--/ewebeditor.