(photo credit: REUTERS)
Long-distance runners and mountain climbers are not the only ones to benefit from altitude training – that is, learning to perform well under low-oxygen conditions. Scientists in Rehovot have discovered that cancer-fighting cells of the immune system can also improve their performance through a cellular version of such a regimen. In a study published in Cell Reports, Weizmann Institute of Science researchers have shown that the immune system’s killer T cells destroy cancerous tumors much more effectively after being starved for oxygen.
Harnessing the immune system to battle malignancy – an approach known as cancer immunotherapy – has already started saving the lives of cancer patients in the past few years. In one major version of this approach, killer T cells are removed from the patient’s blood, grown in a lab dish and adapted to identifying and destroying cancerous cells; they are then returned to the patient’s bloodstream. This method has so far worked best against certain leukemias and lymphomas, but not against solid tumors, possibly because within such tumors, oxygen concentration is extremely low: it accounts for only 0.5% to 5% of the gas dissolved in the extracellular fluid. This is lower than in most healthy organs and certainly much lower compared with levels in a regular lab incubator, in which oxygen accounts for 20% of the gas dissolved in the culture fluid used for growing the cells.
Tumor cells manage to make effective use of glucose, the major cellular fuel, even when oxygen concentration is low. But T cells have a hard time penetrating tumors and performing their killing function. Previous studies had shown that growing T cells under low-oxygen conditions helps them kill other cells in a laboratory dish, but their actual cancer-fighting ability has never been tested.
“Killer T cells are the ones to target and destroy cancerous cells, but they don’t always manage to eliminate the malignancy,” said team leader and immunology Prof. Guy Shakhar. “We’ve shown that by growing these T cells in an oxygen-poor environment, we can turn them into more effective killers.”
In the new study, research student Yael Gropper and staff scientist Revital Zehavi-Feferman from Shakhar’s team, together with Drs. Tomer Meir Salame and Ziv Porat of Weizmann’s Life Sciences Core Facilities Department, and Dr. Tali Shalit of the Stephen and Nancy Grand Israel National Center for Personalized Medicine, put T cells through an altitude training of sorts – by growing them in an incubator with an oxygen concentration as low as 1%. They then divided mice affected by melanoma tumors into two groups; one group was injected with the oxygen-starved T cells, the other with T cells grown under regular oxygen conditions.
Oxygen-starved T cells proved much more effective at fighting the cancer. Mice treated with these cells lived longer and their tumors shrank much more dramatically compared with the mice treated with regular T cells. Surprisingly, the oxygen-starved T cells did not penetrate the tumors better than the regular cells.
Apparently, they fought the cancer more successfully because they had a higher content of a destructive enzyme called granzyme B that penetrates and kills cancerous cells.
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“Just as altitude training increases endurance in humans, so putting killer T cells through a ‘fitness regimen’ apparently toughens them up,” Shakhar explained.
If these findings are confirmed with human T cells, they may provide an immediate means of improving immunotherapy against solid tumors. Shakhar: “In cellular immunotherapy, T cells need to be removed and grown outside the body in any event. Growing them under low oxygen pressure is relatively simple, but this small adjustment to existing clinical protocols may significantly improve the therapy’s effectiveness.”
WOMAN DR. REPLACES WOMAN DR. IN JERUSALEM Dr. Tamar Elram has replaced Dr. Osnat Levtzion- Korach as director-general of Hadassah-University Medical Center on Jerusalem’s Mount Scopus. Elram previously was deputy director-general of Hadassah- University Medical Center in Ein Kerem.
Levtzion-Korach became director-general of Assaf Harofeh (Yitzhak Shamir) Medical Center in Tzrifin.
Elram, a Hebrew University- and Harvard University- trained gynecologist with a degree in medical administration, was born in England and in the last two years ran Meuhedet Health Services’ Misgav Ladach Hospital in Jerusalem. She was also deputy district health officer of Meuhedet.
Hadassah Medical Organization director-general Zeev Rotstein welcomed Elram, saying that she has “returned home to Hadassah” and would surely advance the Mount Scopus hospital further.
BNEI BRAK HOSPITAL ADDS PSYCHIATRIC BEDS A spacious, new 24-bed in-patient women’s ward in the mental health wing of Bnei Brak’s Ma’ayanei Hayeshua Medical Center has accepted its first patients. The hospital’s patient load reflects the backgrounds of city residents of the city, which is largely ultra-Orthodox. Prof. Rael Strous, head of the hospital’s psychiatry department and medical director of the psychiatric wing, said he is committed to fighting the stigma of mental health treatment.
“In the 12 months since we opened the psychiatric wing, we have made a huge impact on the mental health of the community we serve. Thousands of patients already attend our out-patient clinics and day care treatment center, and we continue to expand our in-patient treatment facilities.”
The new director of the women’s ward, Dr Pnina Abramovitz-Shnaider, said at the opening that the new facility represents an important milestone in the hospital’s psychiatric intervention services.
“Ma’ayanei Hayeshua has always championed the sanctity and dignity of human life. By offering our women patients the privacy and dignity they deserve, we will encourage more families to benefit from our highly professional mental health services.”
The hospital’s founder and president, Dr Moshe Rothschild, declared: “Today marks a further stage in the full operation of this now universally-recognized and much-needed therapeutic facility. Mental health is the biggest medical revolution in the past 100 years, and we plan to be at the forefront of this revolution.”
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