A team of immunologists at the University of Massachusetts Amherst has discovered a pre-wired ability in ‘resting’ T cells to remember past viral foes, a promising breakthrough for targeted cancer therapies.
The research, published recently in Science Advances, describes a novel and unusual mechanism for T cells to remember the pathogens and cancers that they had previously encountered. This immunological memory is crucial to the body’s immune response and is the basis of how vaccines work; boosting cellular memory to recognise tumours could help improve cancer therapies.
Our bodies have different types of T cells, which are white blood cells. One type is CD8 T cells, which specialise in fighting both viral pathogens and altered cells of the organism itself, like cancerous tumour cells. Most of the time, the CD8 T cells are ‘naïve’ - mustered out of active duty and resting. But when they recognise foreign antigens after bumping into them, they suddenly wake up, turn into killer CD8 T cells and attack whatever the pathogen may be, from a common cold to cancer. After the killer T-cells have won their battle, most of them die.
“But,” says Leonid Pobezinsky, Associate Professor of Veterinary and Animal Sciences at UMass Amherst and the paper’s senior author, “somehow a few CD8 T cells survive, transform into memory cells and form an elite task force called the ‘memory pool’ - they remember what that particular antigen looked like, so that they can be on the lookout for the next time it invades the body.”
It is these CD8 memory T cells that play critical roles in long-term immune protection and are central to tumour immunotherapies, because they are already primed to go into battle against specific pathogenic invaders. “They are fast to recognise a problem,” says Pobezinsky, “stronger to fight, and already know how to kill the specific threat. They don’t need to be trained.”
Immunological dogma has long held that naïve T cells were ‘undecided’, meaning that it wasn’t until they were exposed to a pathogen that they began the process of transforming into the killer T cells that would die or the ones that would wind up as memory cells, preserving the record of the invading pathogen for the future.
Adam Lynch, a graduate student in Pobezinsky’s laboratory and the paper’s lead author, comments: “What we found runs counter to the long-held belief. There is a small population of naïve T-cells that always turn into memory cells. They are pre-wired to do so.”
Pobezinsky adds that this small population is likely not involved in the direct immune response itself, but serve more as a library, preserving the memory of past pathogens and how to fight them for the future.
Shown above are microscopy images of antigen-inexperienced (‘naïve’) mouse CD8 T cells (green). A subset of these cells expresses Dapl1 protein (red), identifying a population committed to a memory stem-like lineage. Nuclei are shown in blue.
These pre-wired memory cells have stem-cell-like properties, meaning that they easily can turn into other types of T cells involved in the immune response, especially when exposed to the current bath of cutting-edge immunotherapies. The researchers believe these cells could be trained to recognise specific types of cancer long before those cancers appear in a person’s body.
“We haven’t yet discovered these cells in humans,” Pobezinsky notes. “But once we do, we may be able to make them, train them against specific cancers, and use them as the basis for targeted immunotherapies that would let our own body’s immune system identify and destroy cancerous tumours.”
Support for this work was provided by the National Institutes for Health and the National Research Service Award.
- Lynch AC, Hioki KA, Liang X, et al. A Dapl1+ subpopulation of naïve CD8 T cells is enriched for memory-lineage precursors. Sci Adv. 2025;11(34):eadx5687. doi:10.1126/sciadv.adx5687