The term “get high” is usually used to describe marijuana use, but in this case, we’re talking about literal altitude. According to a new study out of the Weizmann Institute of Science, low-oxygen conditions (those encountered at high altitudes) could be just the thing you need to destroy those tumor cells.
The scientists grew a batch of T cells in an incubator set to low oxygen concentration—as low as 1%, in fact. The T cells, also known as “the foot soldiers of cancer immunotherapy,” were injected into mice affected by melanoma tumors. Another batch of mice was injected with regular T cells grown under “normal oxygen conditions.”
The T cells in both groups of mice targeted and destroyed cancerous cells, but it was the oxygen-deprived T cells that really did the job effectively. Not only did they shrink the tumors “much more dramatically,” but they extended the lifespan of the mice that received them.
It’s important to note that the oxygen-starved T cells did not penetrate the cancer cells more effectively than the regular T cells. Tumor cells are able to flourish in low oxygen environments, but T cells are usually less effective at penetrating the tumor cells. Training the T cells to function in low-oxygen environments did not make them more effective at penetrating tumor cells.
However, it did make them more effective at killing off the tumor cells, thanks to the higher content of granzyme B, an enzyme that is able to penetrate and destroy tumor cells. The T cells produced in low oxygen environments produced more of this enzyme, better enabling them to break down the tumor cells.
The T cells produced in low oxygen environments produced more of this enzyme, better enabling them to break down the tumor cells.
The lead author stated, “Just as altitude training increases endurance in humans, so putting killer T cells through a ‘fitness regimen’ apparently toughens them up.”
How can this discovery benefit cancer patients? According to the lead author, “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.”
1. Yael Gropper, Tali Feferman, Tali Shalit, Tomer-Meir Salame, Ziv Porat, Guy Shakhar. “Culturing CTLs under Hypoxic Conditions Enhances Their Cytolysis and Improves Their Anti-tumor Function.” Cell Reports, DOI:http://doi.org/10.1016/j.celrep 2017.08.071.