Cancer-killing T cells are getting help from La Jolla researchers

 Killer T cells surround a cancer cell.
(National Institutes of Health)

Papers from UCSD and the La Jolla Institute for Immunology indicate innovative ways that key immune-system defenders can be made stronger and more effective.


T cells, white blood cells capable of detecting and killing everything from viruses to cancer, are getting a lot of love from researchers in La Jolla.

Papers published in medical journals document techniques for boosting the energy levels of the microscopic defenders and helping them more effectively detect and destroy cancer cells capable of evading standard immune system scrutiny.

A paper published Aug. 30 in the journal Nature from a team of reseachers led by UC San Diego postdoctoral researcher Miguel Reina-Campos discussed how memory T cells that live in human tissue respond to cholesterol.

Studying cells living in the small intestines of mice, a team that included collaborators from several institutions found that cells were affected by the presence of dietary cholesterol, shutting down key internal cellular machinery used to help T cells function.

By manipulating this internal machinery, researchers were able to trigger the production of a substance called coenzyme Q, an antioxidant that is crucial to unlocking energy stores inside cells.

The findings, Reina-Campos said, suggest it is possible to make T cells able to fight longer.

“When T cells are going places that are not very inhabitable, like tumors, we can help them be better adapted for survival,” Reina-Campos said. “It’s important to remember that the more T cells you have, the better protected you are against infections and controlling malignancies like cancer.”

Cancer cell biologist Ana Rosa Saez Ibanez, an associate of the Cancer Research Institute, reviewed the paper and said it has promise to unveil “pharmacological and dietary interventions that could increase protection against infections and enhance efficacy of immuno-oncology treatments.”

A second paper, published online Sept. 1 by the Journal of Clinical Investigation by a team led by immunologist Stephen Schoenberger of the La Jolla Institute for Immunology, describes a new way to design cancer vaccines that can activate two different classes of T cells.

Cancer vaccines use custom-made amino acids to mimic unique markers called “neoantigens” that are known to appear on the surfaces of cancer cells. If designed correctly, these molecules can be picked up by the immune system and used to program “CD8” killer T cells capable of hunting down and destroying tumors.

Some tumors, though, are able to maintain “checkpoint” features on their surfaces that allow them to trick CD8 hunters into disengaging.

Schoenberger’s team, also working with mice, found that certain neoantigens are capable of activating not just CD8 hunters but also a sort of helper “CD4” T cell.

Having both engaged simultaneously, the researcher said, helps broaden the targeting of CD8 cells, making hits on target more likely.

“It’s harder for a tumor to evade a collection of guided missiles than it is a single specificity,” Schoenberger said.

Saez Ibanez said the Cancer Research Institute “believes these findings could effectively be applied to the development of more efficacious personalized cancer vaccines that can expand the range of tumors responsive to immunotherapy.” ◆