Dr. Reina sits in his laboratory. He is wearing a white lab coat and looking at the camera
LJI Assistant Professor Miguel Reina-Campos, Ph.D.

T cells can sense testosterone—What does that mean for prostate cancer therapies?

The future is bright for prostate cancer research. It’s glowing, in fact, thanks to new tools that combine the eye-catching fluorescence of microscopy with next-generation sequencing tools. 

LJI Assistant Professor Miguel Reina-Campos, Ph.D., specializes in using spatial transcriptomics tools to advance the field of tissue immunology. Spatial transcriptomics gives scientists a way to track where immune cells are located (the “spatial” part) and exactly how those immune cells are trying to protect the body (the “transcriptomics” part).

Microscopy image with a background. Cells are colored in shades of pink, blue, orange, green, red, and blue to depict differences in gene transcription.
An image produced through Xenium analysis of mouse small intestines. Protruding “villi” stick up from the lining of the small intestine. Valley-like “crypts” fill in the gaps.
In a recent study, Dr. Reina-Campos and colleagues used spatial transcriptomics tools to track the movement of T cells through tissues in the gut.

By tracking this immune-cell activity, Dr. Reina-Campos can help guide the development of new immunotherapies for prostate cancer, a disease that kills around 35,700 men each year.

“No one has ever profiled tissues like this before,” says Dr. Reina-Campos. “Spatial transcriptomics enables us to look at hundreds of thousands of cells and thousands of genes in prostate tissues.”

When you take away testosterone

Already, Dr. Reina-Campos has shown the power of spatial transcriptomics in studying T cells that fight pathogens in the gut. He has also developed a promising approach for powering up T cells to better fight tumors.

Now Dr. Reina-Campos is investigating how specialized “tissue-resident memory CD8+ T cells” fight prostate cancer. 

Scientists know these T cells have the power to kill tumor cells. But T cells don’t work alone. They interact with other immune cells, and they can sense a huge range of signaling molecules, including testosterone and estrogen. These signaling molecules direct T-cell activity, including antitumor activity.

So what happens if you need to fight a tumor, but you suddenly take away testosterone?

“The standard of care for prostate cancer is androgen deprivation—or ‘chemical castration’—in which you reduce testosterone levels almost to zero,” says Dr. Reina-Campos. “But the role of testosterone and its sensor, which is an androgen receptor on immune cells, is not really well known.”

Scientists need to know how androgen deprivation affects cancer-fighting T cells. With spatial transcriptomics, Dr. Reina-Campos can track T-cell activity before and after androgen deprivation. He can uncover exactly which kinds of T cells jump into action and how those T cells travel through tissues to find their targets.

Dr. Reina working in the lab. He is wearing a white lab coat and blue gloves
LJI Assistant Professor Miguel Reina-Campos, Ph.D.

Prostate cancer research may be just the beginning. Dr. Reina-Campos is looking forward to working closely with collaborators, here in San Diego and across the country, to understand how skyrocketing estrogen levels during pregnancy affect T-cell activity in mammary tissue. 

Dr. Reina-Campos is also contributing to UC San Diego and Salk Institute studies into how immune cells guard the placenta to stop disease at what scientists call the maternal-fetal interface.

“This research follows T-cell function all through the monthly cycle, all the way through pregnancy and giving birth—which is when hormone levels really change,” says Dr. Reina-Campos. “This is part of trying to understand the underlying mechanisms of the immune system.”

With spatial transcriptomics, Dr. Reina-Campos can track how T cells move, like glowing constellations, through our tissues. This is a new kind of cartography, a mission that may guide us toward better medicine for all.