It's time to say goodbye to ineffective and costly cancer treatments. Japanese scientists have found unique genetic alterations that could indicate whether expensive immune checkpoint inhibitors would be effective for a particular patient.
Programmed-death ligand 1 (PD-L1) is a protein that tells the immune system not to kill a particular cell. Publishing in Nature, a recent study reports that genetic alterations affecting a part of the PD-L1 gene increases the production of the protein, allowing cancer cells to escape detection by the immune system.
Japanese scientists have found unique genetic alterations that could indicate whether expensive immune checkpoint inhibitors would be effective for a particular patient. Publishing in Nature, the study reports that genetic alterations affecting a part of the PD-L1 gene increases the production of the protein, allowing cancer cells to escape detection by the immune system.
Credit: Kyoto University
"This is the first study to illustrate that a structural abnormality in the 3' untranslated region of the PD-L1 gene causes an abnormally high production of PD-L1 protein, consequently aiding cancer immune escape," says one of the lead authors, 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."
Antibodies that target PD-L1 or its receptor PD-1 have shown remarkable therapeutic effects 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.
"We identified PD-L1 structural alterations affecting the 3' untranslated region of the PD-L1 gene in 27% of patients with adult T-cell leukemia/lymphoma by analyzing next-generation sequencing data," explains senior author Seishi Ogawa.
Prompted by this initial finding, the team searched for similar structural alterations in sequencing data from a total of 10,210 samples deposited in the Cancer Genome Atlas.
"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. We also generated human and mouse cells having a similar structural alteration using the CRISPR-Cas9 genome editing system, and confirmed that these cells actually showed an elevated expression of PD-L1 protein and were able to escape the immune attack." says Ogawa.
"To test the importance of such structural alteration as a genetic marker, a phase two clinical trial is ongoing at Kagoshima University and other institutions," adds Ogawa. "Once we confirm the significance of these genetic alterations, it'll be a game-changer for immunotherapy in cancer."
The paper "Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers" appeared May 23, 2016 in Nature, with doi: 10.1038/nature18294
Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at both undergraduate and graduate levels is complemented by numerous research centers, as well as facilities and offices around Japan and the world. For more information please see: http://www.
Anna Ikarashi | EurekAlert!
Antibiotic effective against drug-resistant bacteria in pediatric skin infections
17.02.2017 | University of California - San Diego
Tiny magnetic implant offers new drug delivery method
14.02.2017 | University of British Columbia
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
17.02.2017 | Medical Engineering
17.02.2017 | Medical Engineering
17.02.2017 | Health and Medicine