Starving cells of oxygen can help them kill cancers, Israeli researchers find

Growing ‘killer T cells’ with less oxygen, like mountain climbers, makes them deadlier in targeting cancer cells, Weizmann Institute scientists show

Illustrative: Cancer cells. (Pixabay)
Illustrative: Cancer cells. (Pixabay)

Researchers at Israel’s Weizmann Institute of Science have developed a method to reinforce the power of cells that kill cancerous tumors by starving them of oxygen, allowing immunotherapy treatments to be used in targeting previously immune solid tumors.

The research was published in the journal Cell Reports. In the article, the researchers liken the new, toughened cells to athletes who train in high altitudes, where the percentage of oxygen in the air is lower.

The technique is based on removing cytotoxic T lymphocytes (CTLs) from the body and then breeding them in a lab, after which they are reintroduced into a patient’s blood stream. The CTLs, known also as killer T cells, are cells in charge of destroying damaged cells, cancer cells, and cells infected with viruses or other pathogens.

In this immunofluorescence image, a group of killer T cells (outer three) is engaging a cancer cell (centered one). A patch of signaling molecules (pink) that gathers at the site of cell-cell contact indicates that the CTL has identified a target. Lytic granules (red) that contain cytotoxic components then travel along the microtubule cytoskeleton (green) to the contact site and are secreted, thus killing the target. (The National Institutes of Health / Wikipedia)

Quoted on Wednesday by Medical News Today, senior Weizmann Institute researcher Guy Shakhar compared the oxygen-starved killer T cells to mountaineers who gradually get used to lower oxygen levels. “Just as altitude training increases endurance in humans, so putting killer T cells through a ‘fitness regimen’ apparently toughens them up,” he explained.

“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,” Shakhar said. “We’ve shown that by growing these T cells in an oxygen-poor environment, we can turn them into more effective killers.”

Guy Shakhar (Weizmann Institute)

Until now, treatment using T cells, known as cancer immunotherapy, has so far been only efficient in treating leukemias and lymphomas.

When tackling solid tumors, the method has so far proven ineffective, since these tumors typically have a very low percentage of oxygen – about 5 percent – far lower than the conditions under which the T cells are grown in labs (typically 20%).

An experiment by Shakhar’s and his team has shown the low-oxygen T-cells, or hypoxic CTLs, to have a higher success rate in controlling tumors introduced in laboratory mice. A control group included mice not injected with any T cells.

The team found that the hypoxic CTLs proved much better at combating the tumors than CTLs grown under normal lab conditions (i.e. with normal oxygen levels).

The low-oxygen cells used in the experiment were grown in an incubator with an oxygen concentration of just 1 per cent.

The lowest oxygen percentage for which athletes train is 6.9 per cent – what climbers feel at the top of Mount Everest.

The Weizmann Institute of Science in Rehovot. (Doron Horowitz/Flash90)

Mice treated with the hypoxic T cells lived longer and their tumors shrank much more dramatically compared with the mice treated with regular T cells, the experiment showed.

Shakhar and his team noted that the cells’ ability to penetrate the tumor cell walls — with a protein called perforin — was not increased, but that after penetrating the malignant cells, the T cells’ punch was much deadlier, since the enzyme that battles the diseased cells became much stronger in the oxygen-low conditions.

One of the reasons for the dramatic improvement in the T cells’ ability to fight the malignant cells is that in solid tumors, the oxygen percentage inside the tumor is indeed much lower than in cancers of the blood or lymph glands.

According to a report on a website affiliated with the Weizmann Institute, studies have shown that growing T cells under low-oxygen conditions helps them kill other cells in a laboratory dish, but their actual cancer-fighting ability had never been tested before, until now.

The team now awaits to implement the treatment in humans to verify its efficiency.

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