Exhausted immune cells bear distinct genetic signatures, and may be difficult to revive — a finding with implications for therapies that harness the cells.
Immune cells called T cells can become 'exhausted' and dysfunctional after exposure to cancer or chronic infection. Two teams — one led by John Wherry at the University of Pennsylvania in Philadelphia, the other by Nir Yosef at the University of California, Berkeley, and Nicholas Haining at the Dana-Farber Cancer Institute in Boston, Massachusetts — looked at changes in gene expression and epigenetic markers (chemical changes to DNA that do not affect its sequence) in mice infected with a virus. They found that exhausted T cells had a characteristic profile that distinguished them from functional T cells.
One of the teams also showed that exhausted T cells were reactivated by an antibody that blocks PD-L1, a protein that suppresses T-cell responses. However, this effect was transient when viral levels remained high, suggesting that certain kinds of immunotherapy may need to be combined with other treatments to yield lasting benefit.