AsianScientist (Jun. 13, 2016) – A unique genetic alteration that increases the production of a protein called programmed-death ligand 1 (PD-L1) allows cancer cells to evade attack from the immune system. The results, discovered by scientists in Japan, were published in the journal Nature.
Antibodies that target PD-L1 or its receptor PD-1 have shown remarkable therapeutic efficacy for many cancer patients, sometimes even for those who are terminally ill. Treatment using such antibodies is extremely expensive, however, and oncologists are keen to find a biomarker that can predict the effectiveness of these drugs for individual patients.
“This is the first study to illustrate that a structural abnormality in the PD-L1 gene causes an abnormally high production of PD-L1 protein, consequently aiding cancer immune escape,” said one of the lead authors, Assistant Professor Keisuke Kataoka at Kyoto University.
“Our study suggests that whether or not a cancer has this particular abnormality could be a good indicator of its response to immune checkpoint inhibitor drugs.”
By analyzing next-generation sequencing data, the researchers identified PD-L1 structural alterations in 27 percent of patients with adult T-cell leukemia/lymphoma.
Encouraged by this initial finding, the team searched for similar structural alterations in sequencing data from over 10,000 samples in the Cancer Genome Atlas, an online portal of publicly available cancer genomic data.
“Through this analysis, we found that such abnormalities were found in many common cancer types, including malignant lymphoma, as well as stomach and cervical cancers,” said senior author Professor Seishi Ogawa.
After generating human and mouse cells with similar structural alterations in PD-1, the researchers confirmed that the cells were able to evade detection by the immune system.
The article can be found at: Kataoka et al. (2016) Aberrant PD-L1 Expression Through 3′-UTR Disruption in Multiple Cancers.
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Source: Kyoto University.
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