Nature https://doi.org/10.1038/s41586-018-0130-2 (2018)
The immunological-checkpoint therapy used for cancer operates mainly by unleashing the effector function of cytotoxic T lymphocytes. In Nature, Newell and colleagues examine human colon and lung tumors and find that tumor-infiltrating lymphocytes (TILs) are very heterogeneous. Not only are there TILs specific for the tumor, as expected, but also there are large numbers of TILs present that are not specific for tumor antigens, and some of these bystander TILs are even specific for viral antigens. These two categories of TILs have distinct phenotypes: the tumor-specific TILs express the ATP ectonucleotidase CD39 and have a chronically activated and exhausted signature, whereas the bystander TILs lack CD39 and signs of exhaustion. CD39 might therefore serve as a useful biomarker for the isolation of tumor-specific cytotoxic T lymphocytes.