02/13/2020 | News release | Archived content
Identifying patients who will, won't benefit from 'immune checkpoint therapy'
The team created a new way to determine which patients are most likely to benefit from a treatment known as immune checkpoint therapy, where drugs like pembrolizumab and nivolumab are used to dodge the barriers that some cancer cells use to evade the immune system. It's one of many ways that physicians are exploring the use of immunotherapy to spur the body's natural defenses to fight cancer.
Currently in endometrial cancer, physicians use a measurement known as 'Mismatch Repair Deficient' (dMMR) to determine which patients are most likely to benefit. Based on the measurements of immune activity in this study, the scientists have proposed a new measure focused on a patient's 'antigen presentation machinery,' or APM. The APM describes how well the body flags cancer cells and presents them to the body's immune system for destruction - a key function for checkpoint inhibitors to be effective.
Better insight into exactly who would benefit from the drugs would allow physicians to avoid their use in patients who are unlikely to benefit, sparing those patients severe and unnecessary side effects.
'This is hypothesis-generating research,' said Karin Rodland, one the corresponding authors and a cancer biologist at the Department of Energy's Pacific Northwest National Laboratory. 'It's like the moon mission, where the crew brought back rocks for study by many other scientists. Here, we are providing the raw information for scores of scientists to pore over, to study and to generate new hypotheses. Eventually we hope this information will lead to clinical trials and perhaps new ways to treat this disease.'
The team has made all the data accessible to researchers in a web tool called LinkedOmics, which also provides computational tools for further exploration of this dataset.
'This resource will enable broad usage of the data for new discoveries in endometrial cancer research,' Zhang said.
This work was supported by grants U24CA210955, U24CA210954, U24CA210972, U24CA210979, U24CA210986 and U01CA214125 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC), by grant RR160027 from the Cancer Prevention & Research Institutes of Texas (CPRIT), and by funding from the McNair Medical Institute at the Robert and Janice McNair Foundation. The measurements of proteins and protein activity were done at EMSL, the Environmental Molecular Sciences Laboratory, a user facility funded by the DOE's Office of Science and located at PNNL.