Research shows how T-cells are blocked from fighting cancer

Researchers at Salk Institute have uncovered a key insight about how oxidized fat molecules inhibit T-cells from killing cancer cells.

Their recent discovery, which was published in the peer-reviewed journal Immunity, discusses ways to make sure the immune system can effectively fight cancer by “reducing the oxidative lipid damage in killer T-cells,” according to a Salk news release. The research can help with the development of immunotherapies for cancer.

“The newest drugs today that are revolutionizing cancer treatment are called immunotherapies,” Susan Kaech, a Del Mar resident and professor who led the research, said in an interview. “They’re targeting these t cells to try to make these t cells wake up and become more activated to fight cancer.”

Kaech’s daughter, Jaden Shadel, made an illustration that shows how the bad fat inhibits T-cells.

(Illustration by Jaden Shadel)

As part of the immune system, T-cells play a role in fighting infections, including COVID-19.

“But they also can play an important role fighting cancer,” said Kaech, who has been with Salk Institute for about three years. “Normally, our immune system is not equipped with the ability to fight cancer because the tumors themselves are very immunosuppressive and they kind of shut down the immune response and the T-cells— when they enter the tumor, they get shut down and they get suppressed.”

The researchers saw that tumors had larger amounts of oxidized lipids, commonly referred to as bad fat, according to the news release.

“It illuminated a new way in which these T-cells can become impaired when they infiltrate the tumors,” Kaech said, adding that “how they become impaired is a very big area of cancer research.”

They observed how certain types of T-cells were neutralized by those oxidized lipids.

“We found that when the T-cells get ‘stressed out’ by oxidized lipids, they shut down their anti-tumor functions,” Shihao Xu, a postdoctoral fellow at Salk and the first author on the paper, said in a statement.

Kaech, who earned a Ph.D. in developmental biology at Stanford University and worked at Yale, added that researchers have been “trying to understand this mechanism of how T-cells become impaired in the tumors when they infiltrate the tumors.”

“The tumor microenvironment contains a lot of this oxidized fat, and the T-cells are taking it up, they’re engulfing it, and when they do that it suppresses their ability to be functional and to fight the cancer,” she said. “So it’s a pretty exciting new development in terms of our understanding of a metabolic way in which t cells can be physically suppressed within tumors.”