A major breakthrough! Two Cell studies map the immune cells of brain tumors!

June 1, 2020 /
BiovalleyBIOON / - Researchers from the Ludwig Cancer Research Center and the University of Zurich (UZH) and the University Hospital of Zurich (USZ) recently studied the types and locations of immune cells in brain tumors The results show that there are great differences in the types, location and function of immune cells in different sources, different types and even the same type but different levels of brain tumors, which provide the basis and guidance for the personalized treatment of different brain tumors, and the results of the two related studies were published recently in Cell Cellin the first study,, researchers from the Ludwig Cancer Research Center used a comprehensive comparative analysis to describe the different immunologicalcharacteristics of tumors (i.egliomas) and
tumors that are transferred from the lungs, breasts and skin to the brainThe researchers analyzed in detail the function, location, and characteristics of different immune cells in thetumormicroenvironment (TME), which inhibit immune attack, support cancer cell growth, and promote cancer progressionThe study was entitled "The Pheon of The Microenvironmental Landscape in Brain Sinstitutes Reveals Disease-Specific Brains of Immune Cells"picture source: Cellstudy leader johanna Joyce, a member of Ludwigshalos, said: "Comparing thesetumors, we can see very clearly the difference sizout not only between primary and metastatic brain cancers, but also between high-level and low-level gliomas, and the differences between metastatic tumors at different primary sitesWithout putting these different disease entities together, we won't be able to see how different their immune systems are"
cancers selectively utilize a variety of immune cells and even manipulate their gene expression procedures, allowing them to suppress anti-tumor immune responses, help metastasis, build blood supply and provide other critical supportTargeting these metamorphic immune cells, or "re-educating" them to attack theof the hosttumors, is a major focus of the currentof immunologycancerJoyce said: "Our results highlight that we cannot take a universal approach to brain cancerIn their study, Joyce and her colleagues looked at the number and primary location of 14 immune cells in 100 brain tumor samples taken from patientsThey also analyzed the full spectrum of proteins in the sample and the overall gene expression patterns of individual immune cellsThey then combined these detailed, large-scale analyses to map the types of immunein eachtumor and capture differences in their inherent immune cell functionthis comparative analysis reveals five types of immune cells that primarily act on the brain's TME: macrophages derived from mononucleosis entering the brain from other parts of the body; small glial cells -- resident macrophages in the brain; associated bone marrow cells called neutrophils; CD4-T cells, which coordinate and regulate immune responses; and CD8 plus (killing) T cells that destroy cancer cells and can be activated by checkpoint-blocking immunotherapyThe specific composition of the immune system and the functional state of the cells that make up the cells are formed by the interaction of the brain's unique biology with the innate characteristics of each tumor "We have to look at these brain malignant tumor
s from a different perspective, " Joyce said "We can't just put them together and hope that some kind of therapy will treat all these diseases "
, for example, this study shows that melanoma(one of the few brain tumor
s that respond to checkpoint blocking) contains a large number of T-cells Gliomas are rich in macrophages and small glial cells, with few T cells "As you can imagine," Joyce says, "you're going to want to develop a treatment for gliomas that increase the entry of T-cells into the microenvironment." "On the other hand, for melanoma brain metastatic tumors, the main goal is to activate existing T cells in TME to attack cancer cells there are differences even within gliomas The researchers found that small glial cells dominate low-grade gliomas, which are characterized by mutations in an enzyme called IDH Higher levels of glioma or glioblastoma (GBMs) associated with the normal IDH gene have more macrophages from blood circulation to brain TME Joyce said: "The treatment that blocks macrophages from leaching the brain may be better at treating high-level gliomas than removing small glial cells." "Furthermore, "re-education" macrophages to attack cancer cells rather than promote cancer cells therapies may prove to be effective in general for gliomas -- a possibility that Joyce's lab is exploring these findings also open up exciting new areas for research For example, large numbers of neutrophils have been found in brain metastasis breast cancer Previous research by Joyce's lab has found that these cells play an important role in the lung metastasis of breast cancer Joyce and her team are now exploring how neutrophils affect their growth in the brain in the second study, , a team of researchers from the University of Zurich (UZH) and the University Hospital of Zurich (USZ) also found different immune cells in different types of brain tumors through single-cell mapping of brain cancer tissue These very accurate "tumor maps" are essential for better understanding the individual immune components of tumor and for developing targeted immunotherapies that activate immune defense responses "Single-Cell M
app
ing of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes"。 removal of malignant brain tumors is a balance between removing as many tumor tissues as possible and protecting healthy tissue Because cancer cells are immersed in healthy brain tissue, it is often not possible to completely remove brain tumors during surgery After surgery to remove as many tumors as possible
the prognosis can be improved by subsequent radiotherapy and chemotherapy, but traditional treatments are difficult to cure Photo Source: "Our immune system is very precise and effective, " says Burkhard Becher of the Institute of
of Immunology at the University of Zurich the University of Zurich Immune defense destroys individual tumor cells while protecting healthy cells "Immunotherapy has been an amazing success in treating certain types of cancer, but for malignant brain tumors, immunotherapy has so far been disappointingly effective One reason is that previously the composition of tumor tissues in brain tumors, especially with regard to immune cells, was not studied in sufficient detail To analyze immune cells in malignant brain tumors, the researchers analyzed tissue from the USZ Neurosurgery Room using a method established at UZH called high-dimensional cell count This technology makes it possible to analyze millions of different cell types simultaneously at a single cell level There are many proteins on and inside cells that vary depending on the cell type Researchers can process large amounts of data using complex, self-learning computer algorithms "For each brain tumor, our technique gives individual characteristics of immune cells This allows you to compare similarities and differences between patients and tumor types "
studies have shown that the main factor determining the type, frequency and distribution of immune cells in individual brain tumors is the type of tumor "Gliomas occur directly in the brain, unlike the metastasis of other tumor
s that spread to the brain in the body In gliomas, we can also make a clear distinction between different subgroups by the specific composition of immune cells," added Ekaterina Friebel and Konstantina Kapolou, both doctoral students in the collaborative research team , according to USZ neurosurgeon Marian Christoph Neidert, the findings not only help to better understand the immune mechanisms of brain tumors: "They also provide the basis for the development of immunotherapy for different types of brain tumors "The tumor tissue in the study came from patients at the USZ Brain Oncology Center However, further research is needed before patients with brain tumors can benefit from research in immunology (BioValleyBioon.com) References: Mapping immune cells in brain tumors
Ekaterina Friebel et al, Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specify of Tissue-Invading Leukocy
, Cell (2020) DOI: 10.1016/j.cell.2020.04.055
Study charts the immune landscape of the brain multiple cancers
Florian Klemm et al.
The of The Brains of The Microenvironmental Landscape in Brain Tumors Reveals Disease-Specifics of Immune Cells Cell (2020) DOI: https://doi.org/10.1016/j.cell.2020.05.007