Michail Sitkovsky, an immunophysiology expert at Northeastern, and his research colleagues have found that supplemental oxygenation could shrink tumors and improve cancer immunotherapy
Michail Sitkovsky, an immunophysiology expert at Northeastern University, and his research colleagues have made a breakthrough discovery in cancer treatment. The new approach, some 30 years in the making, could dramatically increase the survival rate of patients with cancer, which kills some 8 million people each year.
The findings were published Wednesday in Science Translational Medicine, an interdisciplinary medical journal founded in 2009 by the American Association for the Advancement of Science.
Sitkovsky et al. found that supplemental oxygenation inhibits the hypoxia-driven accumulation of adenosine in the tumor microenvironment and weakens immunosuppression. This, in turn, could improve cancer immunotherapy and shrink tumors by unleashing anti-tumor T lymphocytes and natural killer cells.
"This discovery shifts the paradigm of decades-long drug development, a process with a low success rate," said Sitkovsky, the Eleanor W. Black Chair and Professor of Immunophysiology and Pharmaceutical Biotechnology at Northeastern and the founding director of the university's New England Inflammation and Tissue Protection Institute.
"Indeed, it is promising that our method could be implemented relatively quickly by testing in clinical trials the effects of oxygenation in combination with different types of already existing immunotherapies of cancer."
The paper--titled "Immunological mechanisms of the antitumor effects of supplemental oxygenation"--was the result of a robust interdisciplinary collaboration between doctors and researchers at some of the country's most prestigious universities, hospitals, and medical schools. Co-authors comprised 12 researchers from NEITPI, the Northeastern-based consortium aimed at understanding the underlying causes and molecular mechanisms of inflammation; Barry Karger, the director of Northeastern's Barnett Institute of Chemical and Biological Analysis; and doctors from the University of Pittsburgh School of Medicine, the University of Miami Miller School of Medicine, Brigham and Women's Hospital, and the Dana-Farber Cancer Institute, where Sitkovsy holds an appointment as a presidential scholar.
The findings build upon Sitkovsky's previous research and represent the culmination of his life's work, which has been supported by Northeastern and the National Institutes of Health. In the early 2000s, Sitkovsky made an important discovery in immunology, which has come to inform his research in cancer biology. He found that a receptor on the surface of immune cells--the A2A adenosine receptor--is responsible for preventing T cells from invading tumors and for "putting to sleep" those killer cells that do manage to enter into the tumors.
His latest work shows that inhaling 40 to 60 percent oxygen--air offers 21 percent oxygen--weakened tumor-protecting signaling through the A2A adenosine receptor and awakened T cells that had gained the ability to invade lung tumors.
"Breathing supplemental oxygen opens up the gates of the tumor fortress and wakes up 'sleepy' anti-tumor cells, enabling these soldiers to enter the fortress and destroy it," Sitkovsy explained. "However," he added, "if anti-tumor immune cells are not present, oxygen will have no impact."
Sitkovsky further noted that the effects of supplemental oxygenation might be even stronger in combination with a synthetic agent that he calls "super-caffeine," which is known to block the tumor-protecting effects of the adenosine receptor. He and Graham Jones, professor and chair of Northeastern's Department of Chemistry and Chemical Biology, are currently collaborating to design the next generation of this drug, which was originally developed for patients with Parkinson's disease.
"The anti-tumor effects of supplemental oxygen can be further improved by the natural antagonist of the A2A adenosine receptor, which happens to be the caffeine in your coffee," Sitkovsky said. "People drink coffee because caffeine prevents the A2A adenosine receptor in the brain from putting us to sleep."
Casey Bayer | EurekAlert!
Cholesterol-lowering drugs may fight infectious disease
22.08.2017 | Duke University
Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy