Mountain climbers and endurance athletes are not the only ones to benefit from altitude training - that is, learning to perform well under low-oxygen conditions. It turns out 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, researchers have shown that 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 laboratory 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: 0.5% to 5% of the gas dissolved in the extracellular fluid - lower than in most healthy organs, and certainly much lower compared with 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 don't seem to mind the shortage; they manage to make effective use of glucose, the major cellular fuel, even when oxygen concentration is low. But the same is not true for T cells, which 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 foot soldiers of cancer immunotherapy, they are the ones to target and destroy cancerous cells, but they don't always manage to eliminate the malignancy," says team leader. "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 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 did the regular cells. Apparently, they countered the cancer more successfully because they had a higher content of the destructive enzyme, known as granzyme B, that penetrates and kills cancerous cells.
"Just as altitude training increases endurance in humans, so putting killer T cells through a 'fitness regimen' apparently toughens them up," team lead says.
If these findings are confirmed with human T cells, they may provide an immediate means of improving immunotherapy against solid tumors. Explains the team lead: "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."
https://wis-wander.weizmann.ac.il/life-sciences/altitude-training-cancer-fighting-cells
http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31213-5
Oxygen starved immune T cells shrink tumors
- 2,717 views
- Added
Edited
Latest News
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Addressing both flu and COV…
By newseditor
Posted 26 Mar
How the brain senses body p…
By newseditor
Posted 26 Mar
Other Top Stories
Omega-3 may block psychosis years later
Read more
A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerat…
Read more
Sleep apnea and brain damage
Read more
PTSD could be prevented by blocking memory consolidation pathway!
Read more
Body fat hormone leptin influences runner's high
Read more
Protocols
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Profiling native pulmonary…
By newseditor
Posted 08 Mar
Publications
Integrated plasma proteomic…
By newseditor
Posted 27 Mar
APP antisense oligonucleoti…
By newseditor
Posted 27 Mar
Targeting Erbin-mitochondri…
By newseditor
Posted 27 Mar
Regulation of Zbp1 by miR-9…
By newseditor
Posted 27 Mar
Pain-free oral delivery of…
By newseditor
Posted 27 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar