Big Ideas

Clare Yu, Ph.D.

The Unheralded Teammates

In sports, the star of the team always gets the attention. Sure, they’re putting points on the board and getting interviewed after the game. But in any team sport, no star can win without the teammates who are doggedly doing their part in the background. In the world of cancer research, T cells are the stars. They kill cancer cells and score the points for the immunotherapies that have become the hottest trend in the field. Yet there are other, often overlooked, teammates that could be critical to leading the T cells to success: B cells.

Clare Yu, Ph.D., of the University of California, Irvine, is part of an interdisciplinary team of researchers studying how the spatial arrangement of T and B cells in a patient’s tumor affects their prognosis. Her team’s discoveries highlight the importance of the immune cells’ location and underscore the need for a closer look at how B cell teammates support the star players.

Yu, who received a Designated Grant from the V Foundation in 2015 (which was made possible in partnership with Stand Up 2 Cancer), teamed up with Peter Lee, M.D., and his team from City of Hope to take a look at how immune cells are spread inside a tumor. Their idea was the placement of these cells and the interactions among different cell types might influence how well a patient responds to immunotherapy.

Studying the Tumor Microenvironment

“We wanted to think of cancer and the tumor as an ecosystem,” said Yu. “A tumor isn’t just a bunch of cancer cells. They’re in an environment with many different kinds of cells, including cancer cells, immune cells, cells that make fibers, and so on. That’s the tumor microenvironment.”

The team studied the tumor microenvironments of patients undergoing immunotherapy, a treatment that teaches T cells to seek and destroy cancer. Looking at triple negative breast cancer, one of the most aggressive forms of the disease, the team uncovered a clear correlation: When T and B cells were more clumped together or aggregated inside the tumor, there was a higher probability that the tumor would recur. Meanwhile, if the immune cells were more spread out, the prognosis was much better, and the cancer was less likely to come back.

That discovery led Yu to an important question: Are B cells doing more than previously thought?

Looking to the Future

“B cells are famous for making antibodies, but they also do other things like secrete chemicals to tell other immune cells what’s going on, or find a little piece of bad proteins called antigens, and show them to the T cells and say ‘Hey, you should take a look at this, something bad is going on,’ ” said Yu.

We know that prognosis is better when they are spread out, but we don’t yet understand why they are where they are. If we understood these things better, we could make drugs and treatments to help direct the placement of immune cells.

Clare Yu, Ph.D.

Yu said she hopes her work will lead to further studies on the role of B cells in tumors, a line of inquiry that will undoubtedly rely on research teams that combine multiple areas of expertise.

“I think the future of cancer research is more of these convergence themes and interdisciplinary teams, because you get new perspectives and different ways of looking at things,” said Yu. “That leads to new techniques and new tools that can be used not only in the lab, but in the clinic as well.”

Yu, who is herself a breast cancer survivor, said she hopes continued research will lead to cancer becoming something manageable and treatable and doesn’t come with the fear of a death sentence.

“There would be a lot more hope and not as much fear,” said Yu.

More hope. Less fear. Now THAT would be a Victory Over Cancer®.