Stem-Like Memory T Cells Are Discovered
Stem-cell-like memory cells have physical characteristics of very young immune cells. They still have the potential to differentiate and become many different types of immune cells, making them extremely valuable.
T cells are the white blood cells that are the body’s first line of attack against foreign invaders. When designing immunotherapies to treat cancer the goal is to prolong the immune response of T cells a bit beyond what the body normally does when a bacterium or a virus is encountered. Nicholas P. Restifo, M.D., working with Luca Gattinoni, M.D., and other colleagues in CCR’s Surgery Branch recently discovered a subset within the human T cell population that may help clinicians to do just this.
Restifo and Gattinoni and other collaborators reported in a recent paper in Nature Medicine that they have identified a highly undifferentiated stem-cell-like T cell within a patient’s immune system that is capable of continually refreshing itself for long periods of time, perhaps even permanently.
The researchers started with highly undifferentiated T cells and, working within this group, they isolated the tiny fraction showing the first changes in gene expression that occur when T cells make a memory response – that is, when they ‘remember’ antigens they have seen previously and quickly prepare to react.
Their success was built upon previous findings in mice, which showed that T cells acquire stem-cell-like behavior when they are stimulated in the presence of drugs designed to mimic an important signaling pathway called Wnt. The scientists adapted this approach to generate and characterize candidate stem-cell-like T cells in humans.
Restifo and his team then studied blood samples from over 100 healthy human donors and cancer patients in total, to confirm that such stem-cell-like T cells naturally occur in human beings. They successfully did so and also discovered that these stem-cell-like T cells have a superior proliferative capacity and trigger more effective anti-tumor responses in a humanized mouse model.
Because Restifo and his colleagues have identified the genetic characteristics of stem-cell-like T cells, they now may be able to manipulate certain genes to regenerate younger T cells from older ones, which would help advance both immunotherapy and regenerative medicine.Summary Posted: 09/2011
L Gattinoni et al. A human memory T-cell subset with stem cell-like properties. Nature Medicine. Online Sept. 18, 2011. http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2446.html Reviewed by Donna Kerrigan