Researchers Identify Mechanism Underlying Cancer Cells' Immune Evasion
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Researchers identify mechanism underlying cancer cells' immune evasion:
Researchers in China have discovered how brain cancer cells increase production of a key protein that allows them to evade the body's immune system. The study, which will be published August 27 in the Journal of Experimental Medicine (JEM), suggests that targeting this cellular pathway could help treat the deadly brain cancer glioblastoma, as well as other cancers that are resistant to current forms of immunotherapy.
[...] In the new study, Lyu and colleagues, including co-senior author Zhimin Lu from Zhejiang University School of Medicine, identified two cell-signaling pathways that drive the production of PD-L1 in glioblastoma cells. These two pathways, known as Wnt signaling and EGF signaling, stabilize a protein called -catenin, allowing it to enter the cell nucleus and activate the gene encoding PD-L1.
[...] The researchers found that glioblastoma patients with mutations activating this signaling pathway show increased levels of PD-L1 and reduced numbers of T cells within their brain tumors. "Our data demonstrates that EGF and Wnt signaling, which is often active in a wide variety of cancers, induce the upregulation of PD-L1," says Lyu. "Our results therefore provide a molecular basis for improving the clinical response rate and efficacy of anti-PD-1/PD-L1 immunotherapy in cancer patients."
Journal Reference:
Du, Linyong, Lee, Jong-Ho, Jiang, Hongfei, et al. -Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion, Journal of Experimental Medicine (DOI: 10.1084/jem.20191115)
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