Higher blood levels of an immune system protein predict poor survival prospects for melanoma patients with advanced disease, researchers at The University of Texas M. D. Anderson Cancer Center report today at the annual meeting of the American Association for Cancer Research.
Their finding that elevated levels of interleukin-12 (IL-12) are a marker of poor prognosis also points to a molecular explanation for a long-known risk factor for melanoma patients - older age.
Among 150 patients with Stage III melanoma, the study found that the highest levels of IL-12 are associated with a nearly 5-fold risk of death. Although older stage III patients also had an elevated risk of death, age was not a prognostic factor independent of IL-12.
"Melanoma in some cases can be vulnerable to attack by a patient's immune system," said senior researcher Jeffrey Lee, M. D., professor in M. D. Anderson's Department of Surgical Oncology. "What we've found could be evidence of a dysfunctional immune response that actually fuels the growth of melanoma."
Blood-born IL-12 provides both an accessible prognostic marker and a key connection to other signaling proteins; IL-12 as well as these related proteins already have been targeted by antibody therapies in certain autoimmune disorders, Lee said.
The research team examined age, stage of disease, and IL-12 levels in 658 melanoma patients - 445 with stage I or II disease, 150 with stage 3 and 63 at stage IV.
"First, we found that IL-12 levels increase with age," says first author and study presenter Yun Shin Chun, M.D. The mean levels of the protein increased at every age level above age 40. (See Chart)
Age, disease stage and IL-12 levels were then analyzed separately as prognostic factors. Increases in all three were associated with poor overall survival.
"When we analyzed these three factors together, only stage of disease and IL-12 levels were independent predictors of overall survival," Chun said. Age dropped completely out of the picture. Stage of disease was the most powerful prognostic factor.
Both IL-12 and IL-23 are cytokines, proteins that tell cells and other proteins what to do. Cytokines like IL-12 and IL-23 are particularly vital to immune system function. The general level of a person's immune function declines with age, Lee said, as do the levels of most cytokines. The rise of IL-12p40 with age is a relative anomaly.
Chun, Lee and colleagues are investigating IL-12's connection to the tumor promoting IL-23 and about 30 other cytokines in high-risk melanoma patients. Some of the suspect cytokines, including IL-12 and IL-23, already are targeted by therapies used autoimmune disease, Lee noted.Age Mean level of
Co-authors with Chun and Lee are Yuling Wang, Amy Vo, Huey Liu, Daniel Wang, Jeffrey Gershenwald, Janice Cormier, Merrick Ross, Christopher Schacherer and Dana McClain, all of M. D. Anderson's Department of Surgical Oncology; and John Reveille, of the Department of Internal Medicine, division of Rheumatology, University of Texas Health Science Center at Houston.
Scott Merville | EurekAlert!
New study finds distinct microbes living next to corals
22.05.2019 | Woods Hole Oceanographic Institution
Summit charts a course to uncover the origins of genetic diseases
22.05.2019 | DOE/Oak Ridge National Laboratory
Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...
With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.
Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...
'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.
However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...
Working group led by physicist Professor Ulrich Nowak at the University of Konstanz, in collaboration with a team of physicists from Johannes Gutenberg University Mainz, demonstrates how skyrmions can be used for the computer concepts of the future
When it comes to performing a calculation destined to arrive at an exact result, humans are hopelessly inferior to the computer. In other areas, humans are...
Scientists develop a molecular recording tool that enables in vivo lineage tracing of embryonic cells
The beginning of new life starts with a fascinating process: A single cell gives rise to progenitor cells that eventually differentiate into the three germ...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
22.05.2019 | Life Sciences
22.05.2019 | Life Sciences
22.05.2019 | Physics and Astronomy