Cell milestone: PD-1 can't treat brain tumors. This target is interesting

Diffuse glioma is the most common primary human brain tumor, mainly divided into isocitrate dehydrogenase (IDH) mutant glioma and IDH wild-type glioblastoma (the most aggressive and incurable Type of brain tumor).

Although the immune checkpoint inhibitor PD-1/PD-L1 antibody has revolutionized the treatment of many cancers, a recent phase III clinical trial showed that in recurrent glioblastoma (GBM), PD The -1 antibody showed no therapeutic benefit.

On February 15, in a paper recently published in Cell, scientists from the Dana-Farber Cancer Institute, Massachusetts General Hospital, and Broad Institute reported on a milestone.

Specifically, the molecule called CD161 discovered by the scientists is an inhibitory receptor.

So, what did scientists rely on to discover CD161? The answer is single-cell RNA sequencing (RNA-seq) technology.

In this study, the researchers used single-cell RNA-seq technology to analyze tumor-infiltrating T cells from fresh tumor samples from 31 glioma patients to map the gene expression of these T cells.

In order to determine whether blocking the CD161 pathway can restore the ability of T cells to attack glioma cells, the researchers used two methods to make CD161 ineffective: 1) knock out the gene KLRB1 that encodes CD161; 2) use antibodies to block CD161-CLEC2D pathway.

In glioma animal models, blocking the CD161 pathway can greatly enhance the killing of tumor cells by T cells and improve the survival of experimental animals.

Encouragingly, blocking the CD161-CLEC2D pathway also seems to reduce T cell depletion, which is manifested by reduced PD-1 expression.

Studies have also shown that the CD161-CLEC2D pathway is also associated with many other major human cancer types, including melanoma, lung cancer, colorectal cancer, and liver cancer.

Further analysis showed that very few T cells isolated from gliomas expressed more PD-1 than CD161.

"To sum up, our research shows that CD161-CLEC2D is a new potential target for diffuse glioma immunotherapy.

Reference materials:

1# Nathan D.

2# New immunotherapy target discovered for malignant brain tumors (Source: Dana-Farber Cancer Institute)