September 2016


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Oxygen can impair cancer immunotherapy in mice


The Hampton Roads Messenger 5 Our Health


Join the Hampton Roads Messenger in celebrating 'Fruits & Veggies – More Matters Month'


Researchers have identified a mechanism in mice by which anticancer


immune responses are


inhibited within the lungs, a common site of metastasis for many cancers. This mechanism involves oxygen inhibition of the anticancer activity of T cells. Inhibiting the oxygen-sensing capability of immune cells, either genetically


or pharmacological-


ly, prevented lung metastasis. This research was conducted by Nicholas Restifo, M.D., Center for Cancer Research,


National Cancer Institute (NCI) and others at NCI as well as colleagues at the National Institute of Allergy and Infectious Diseases, both parts of the National Institutes of Health. The findings appeared August 25, 2016, in the journal Cell.


Metastasis is the cause of most cancer deaths. It has long been hypothesized


that the process of


cancer metastasis requires cooperation between spreading cancer cells and the cellular environment to which they spread. A key component of that environment is the local immune system, which can act to fight off invading cancer cells.


The researchers discovered that


T cells, a type of immune cell, contain a group of oxygen-sensing proteins which act to limit inflammation within the lungs. This new research shows, however, that oxygen also suppresses the anticancer activity of T cells, thereby permitting


cancer


cells that have spread to the lungs to escape immune attack and establish metastatic colonies.


“Since the lung is one of the most frequent sites to which cancers spread, we hypothesized


that there be unique immunologic might processes


that aid tumor cells in their ability to establish themselves in the lung. Because oxygen is a pervasive local environmental factor in the lung, we wanted to examine what role oxygen might play in regulating immunity in the lung,” said David Clever, a M.D., Ph.D. candidate who trained in Restifo’s lab, and has now returned to the Ohio State University College of Medicine.


The research team discovered that oxygen-sensing proteins, called prolyl hydroxylase domain (PHD) proteins, act within T cells to prevent overly strong immune responses to harmless particles


that frequently enter the


lung. This protective mechanism also allows circulating cancer cells to get a foothold in the lung. Specifically, the researchers found that PHD proteins promote the development of regulatory T cells, a type of T cell that suppresses


the


activity of other parts of the


immune system. They also found that PHD proteins limit the development of inflammatory T cells and restrain their ability to produce molecules involved in cancer killing.


To test whether PHD proteins promote tumor cells to grow in the lung, the researchers used a “knockout” mouse strain that lacks PHD proteins in


melanoma cells. Strikingly, its T cells. These


PHD-knock-out mice, as well as unaltered normal mice, were injected with


whereas normal mice showed large amounts of cancerous melanoma cells in the lungs, the mice whose T cells lacked PHD proteins showed almost no evidence of melanoma in the lungs.


Given their finding that PHD


proteins suppress the inflammatory immune response in the lung, the researchers


wondered whether


inhibiting them might improve the efficacy of adoptive cell transfer, a type of immunotherapy that harnesses the ability of a patient’s own T cells to recognize and attack cancer. In adoptive cell transfer, T cells are extracted


from a patient’s tumor


tissue, expanded to great numbers in the laboratory, and then administered intravenously into the patient along with a T-cell growth factor, with hopes that these cells will return to sites of cancer and eliminate it.


For these experiments, the


research team expanded the antitumor T cells in the presence of a drug called dimethyloxaloylglycine


(DMOG),


which blocks the activity of PHD proteins. In the lab, the drug treatment improved the cancer-killing properties of the T cells and when administered to mice with established metastatic cancer, the drug-treated T cells were far better at eliminating cancer than untreated T cells. DMOG treatment has also been found to improve the cancer-killing properties of human T cells in other studies. The application of these findings to human adoptive cell transfer immunotherapy clinical trials is being investigated by Restifo’s group.


“Adoptive


immunotherapy opportunity


cell transfer


provides a unique for manipulation of


a patient’s own T cells out of the body,” said Restifo. “Although our finding is in mice, we are eager to test whether disruption of the oxygen sensing machinery in T cells -- with drugs, genetics,


or regulation of


environmental oxygen -- will enhance the efficacy of T-cell mediated immune therapies for cancer in humans.” Cancer.gov


LIVE your life. Let US fight your cancer.


Most people know that eating fruits and vegetables is important for good health, but most of us still aren’t getting enough. This September, the Hampton Roads Messenger is proud to participate in Fruits & Veggies – More Matters Month.


Eating a healthy diet with plenty of vegetables and fruits can help you:


• Lower your risk for heart disease and some types of cancer


• Maintain or reach a healthy weight • Keep your body strong and active


• Here are some ideas to help you and your family fit more fruits and vegetables into your day:


• Keep a bowl of fruit handy where the whole family can see it.


• Cut up fruits and veggies ahead of time so they’re ready for quick, healthy snacks.


• Challenge your family to try a new veggie or fruit every week.


Remember, eating more fruits and veggies can be fun – and it’s worth it!


of your life by simply making healthier food choices,"


Jones,


publisher of the Hampton Roads Messenger.


For more information, hamptonroadsmessenger.com. visit


"You can improve many aspects said Angela


Black Men Are Diagnosed With Prostate Cancer at Twice the Rate of White Men


THIS YEAR: •


• • • •


Prostate Cancer is the 2nd leading cause of cancer related deaths among men in the U.S.


233,000 men will be diagnosed with prostate cancer


29,480 deaths from prostate cancer African American Men:


Are diagnosed with prostate cancer at a rate 60% higher than white males


Are two times more likely to die from prostate cancer than white men.


WHAT YOU CAN DO TO LOWER YOUR RISK: Know Your Family History


Exercise 3x/week; eat a diet high in fiber, fruit, veggies, low in fried food, red meat and processed foods; watch the scale (as recommended by the American Cancer Society).


Get annual prostate cancer screenings starting at age 40 (35 if there’s a family history of prostate cancer)


PSA testing should be done not on its own but should include at


University Proton Therapy Institute today.


hamptonproton.org 757.251.6800 Call the Hampton


minimum a Digital Rectal Exam (DRE)


Don’t just get the test but know your stats, know your PSA numbers for the past three tests and discuss changes in your prostate and urinary flow with your physician.


Prostate cancer diagnosis must be separated from treatment. Men diagnosed with prostate cancer should discuss all available treatment options with their doctor.


“Proton therapy helped me maintain my active lifestyle.”


Donald Sherard, Prostate Cancer Survivor, Chesapeake, Va.


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