A new study using advanced imaging technique sheds light on the role of neurons and immune cells in cancer growth and offers potential novel strategies for cancer therapy.
Glioma is a common, highly aggressive brain cancer with low survival rate. Many components are involved in the growth and spread of glioma. Some of these components include neurons and various immune cells such as microglia, monocyte-macrophages, and T cells.
Growing evidence suggests that communication between neurons and glioma cells causes the progression of brain cancer. Therefore, scientists are interested in examining how neurons and glioma cells interact with each other. Additionally, studying the distribution of immune cells in glioma tumour and growth can help scientists better understand how glioma develops and spreads.
In a study published in Journal of Innovative Optical Health Sciences, researchers from the Huazhong University of Science and Technology adopted the multicolour immunofluorescence technique to examine the distribution of neurons and immune cells and gain insights on the growth and spread of glioma.
Mouse glioma cells were transfected to contain a yellow fluorescent protein (named mAmetrine) to generate mAmetrine-GL261 glioma cells that are suitable to be used for multicolour immunofluorescence imaging. Then, the researchers used multicolour immunofluorescence to examine the distribution of neurons and immune cells in the mAmetrine-GL261 glioma growth.
To investigate the distribution of neurons in glioma tumor and growth, the researchers used antibody Anti-NeuN to label the neurons and confocal imaging to observe brain slices. The results showed that in the tumour core, the neurons were sparsely distributed while mAmetrine-GL261 glioma cells were highly concentrated. This shows that the growth of glioma leads to the decrease in neurons and suggests that the reduced neurons contribute to the spread of glioma.
Hence, the researchers theorized that designing a therapy that prevents the death of neurons and increases the number of neurons could be a viable treatment for glioma.
To measure the distribution and number of immune cells that enter the glioma area, the researchers used mouse brain slices to observe the growth and spread of glioma and quantified the number of infiltrating immune cells (monocyte-macrophages, microglia, and T cells) in three different regions of the brain slice image.
The imaging results showed that there was uneven distribution of monocyte-macrophages, microglia, and T cells in the glioma area. Both monocyte-macrophages and T cells were concentrated in the glioma area during its growth and mainly distributed inside the glioma, whereas there was no significant difference in the quantity of microglia in these three regions. This suggests that while glioma growth had no significant effect on the distribution of microglia in the brain, it triggers monocyte-macrophages to enter the glioma area.
Therefore, targeting drugs to prevent monocyte-macrophage from entering the glioma area might inhibit glioma growth. Moreover, understanding the specific functions of glioma-associated macrophages could contribute to the development of novel immunotherapy for glioma.
The researchers also imaged the mouse brain slice where glioma spreading occurred and examined the presence of glioma cells that were tightly surrounded by monocyte-macrophages in different regions of the mouse brain. They found that a large number of monocyte-macrophages and T cells were present in the glioma area.
The high density of monocyte-macrophages and T cells in glioma growth suggests that fluorescent probes or nanodrugs targeting monocyte-macrophages or T cells can be developed to enable sensitive diagnostic methods and immunotherapy for glioma.
The team’s work has revealed the distribution of neurons and immune cells in the growth and spread of glioma and provided possible new strategies for the development of immunotherapy by targeting key immune cells in the glioma. [APBN]
Source: Peng et al. (2023). Fluorescence imaging analysis of the glioma microenvironment. Journal of Innovative Optical Health Sciences, 16(1), 2245005.