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.

Science http://doi.org/bsdh; http://doi.org/bsdj (2016)