Cell: Tumor immunotherapy can be used to treat malignant brain cancer

February 15, 2021 /--- -- Scientists have identified a new target for a potentially malignant brain tumor immunotherapy, according to a recent paper published in the journal Cell.
scientists at the Dana-Farber Cancer Institute at Massachusetts General Hospital and the Massachusetts Institute of Technology and Harvard University's Broad Institute say they have identified a target as a molecule that inhibits immune T-cell anti-cancer activity.
(Photo Source: Www.pixabay.com) Scientists say the molecule, called CD161, is an inhibitory subject that they found in T cells isolated from fresh brain tumor samples called diffuse gliomas.
gliomas include glioblastoma, the most invasive and incurable brain tumor.
CD161 is activated by a molecule called CLEC2D on tumor cells and brain immunosuppressive cells, according to researchers.
the activation of CD161 weakens the T-cell response to tumor cells.
To determine whether blocking the CD161 pathway restores T-cells' ability to attack glioma cells, the researchers invalidated it in two ways: they knocked out the KLRB1 gene that encodes CD161, and used antibodies to block the CD161-CLEC2D pathway.
in animal models of gliomas, this method enhances the lethal effect of T cells on tumor cells and improves animal survival.
also encouraged researchers because blocking inhibitory pathways appears to reduce the loss of cell-killing function in T-cell failure-T-cells, which has been a major obstacle to immunotherapy.
, dr. Kai Wucherpfennig, director of the research center, said, "We have shown that this pathway is also associated with many other major human cancer types, including melanoma, lung cancer, colon cancer, and liver cancer."
many cancer patients are being treated with immunotherapy drugs that disable "immune checkpoints" where cancer cells use molecular braking to suppress T-cells' defenses against tumors, " he said.
these checkpoints will release the immune system to attack cancer cells.
PD-1 is one of the most targeted checkpoints.
, the latest trials of drugs targeting PD-1 in glioblastoma have failed to benefit patients.
current study, researchers found that T cells from gliomas contain fewer cells with PD-1 than CD161.
results, they said: "CD161 may represent an attractive target because it is a cell surface molecule expressed by the CD8 and CD4 T cell substations (two types of T cells involved in the response to tumor cells), which express CD161 compared to the PD-1 protein."
the current study, researchers say little is known about the gene expression and molecular circuits of immunoT cells that soak glioma but do not stop it from growing.
to open the window to these T-cell circuits, the researchers used new technology to read genetic information in a single cell - a method called single-cell RNA-seq.
they applied RNA-seq to glioma-soaked T-cells in fresh tumor samples from 31 patients and created a "atlas" of ways to regulate T-cell function.
analyzing RNA-seq data, the researchers determined that the CD161 protein encoded by the KLRB1 gene was a potential inhibitor.
then used CRISPR/Cas9 gene editing techniques to instain the KLRB1 gene in T cells and to demonstrate that CD161 inhibits tumor cell killing in T cells.
(Bioon.com) Source: New immunotherapy target discovered for malignant brain tumors Source: Cell (2021). DOI: 10.1016/j.cell.2021.01.022 ,