Northeastern researchers find inhaling supplemental oxygen can awaken Anti-​​tumor cells

North­eastern Uni­ver­sity researchers have found that inhaling sup­ple­mental oxygen,40 to 60 per­cent oxygen as opposed to the 21 per­cent oxygen in air, can weaken immuno-­sup­pres­sion and awaken anti-​​tumor cells. 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.

“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,” explained Sitkovsky, the Eleanor W. Black Chair and Pro­fessor of Immuno­phys­i­ology and Phar­ma­ceu­tical Biotech­nology in the Bouvé Col­lege of Health Sci­ences’ Depart­ment of Phar­ma­ceu­tical Sci­ences and the founding director of the university’s New Eng­land Inflam­ma­tion and Tissue Pro­tec­tion Insti­tute. “How­ever, if anti-​​​​tumor immune cells are not present, oxygen will have no impact.”

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 sup­ple­mental oxygen weak­ened tumor-​​​​protecting sig­naling through the A2A adeno­sine receptor and wakes up the T cells that were able to invade lung tumors.“This dis­covery shifts the par­a­digm of decades-​​​​long drug devel­op­ment, a process with a low suc­cess rate,” Sitkovsy said. “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.”

Sitkovsky 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.