Killing Cancer with Protein Production

Jessica Thaxton, Ph.D.
Jessica Thaxton and her team developed a technique to monitor protein production in T cells and will use the data to explore new ways to make T cells more effective at controlling tumor growth.

T cells could be made into better cancer killers by increasing their protein production

by Alhaji Janneh

A team of scientists from Hollings Cancer Center at the Medical University of South Carolina has developed a new flow cytometry technique that can, for the first time, quantify protein production in T cells. T cells are immune cells that surveil the body and can effectively target and kill cancer cells. However, when T cells are in the vicinity of a tumor, cancer cells sap their energy, leading to a decrease in their protein production. This change leads to T cells losing their tumor-killing ability.

The new technique can be used to monitor protein production in T cells and understand how it becomes depressed in the tumor microenvironment. Interventions could then be developed to restore T cells’ protein production and ability to control tumor growth. The team, led by MUSC Assistant Professor and Hollings Cancer Center Researcher Jessica E. Thaxton, Ph.D., recently reported its findings in a priority brief in Cancer Immunology Research.

“This study reveals our first attempt at trying to understand how T cells undergo the process of making proteins,” explained Thaxton. “Before this paper or before this technology, scientists had very little idea how much protein T cells make. It was a shot in the dark. But now we have quantitative data, and we can begin to ask questions like, ‘Which proteins?’ and ‘How are they made?’”

In the past four years, the team observed more than 50 human tumors, and in most tumors they noticed the existence of T cells that made very little protein. This finding led them to surmise that there are T cells unable to make proteins residing in tumors. According to Thaxton, the new technology will help them to monitor these T cells and reawaken their protein production machinery and cancer-fighting ability.

“This paper establishes that T cells able to make protein in tumors have phenomenal ability to control tumor growth,” said Thaxton. “We ultimately want to remodel the existing T cell population in tumors, and that is where our laboratory is headed.”

To understand protein production in T cells in tumors more fully, the scientists used two different types of signaling molecules: cytokines called IL-15 and IL-2. It has been established in other studies that T cells treated with IL-15 control tumor growth very well, but those conditioned with IL-2 do so poorly. The team found that T cells conditioned with IL-15 were able to make proteins in the tumor microenvironment and in tumors, whereas IL-2-conditioned T cells experienced diminished protein production in tumors.

These results will help scientists to understand how they can reawaken tumor T cells and increase their protein production, thereby enhancing their ability to control tumor growth. Thaxton believes that a simple strategy with a modulator that changes the way that T cells generate energy will allow T cells to experience sustained protein production in tumors and produce more effective immunotherapy treatments for patients.

Thaxton believes that the current study is the very first set of experiments that begins to delineate the role of protein production in antitumor immunity and will continue the research by studying which parts of this regulation are most important for tumor control.

Jessica Thaxton and her team developed a technique to monitor protein production in T cells and will use the data to explore new ways to make T cells more effective at controlling tumor growth.