Guilty bystanders.

We’re learning that tumor-infiltrating lymphocytes (TILs) are a window into the tumor-host interaction, often carrying prognostic information. However, our understanding of these cells and their activities is surprisingly limited. This study extensively characterizes cell surface markers and antigen specificity of CD8 TILs. It turns out that the populations of TILs in colon and lung cancers are quite heterogeneous. In fact, up to half of these aren’t even cancer-specific. These “bystanders” express PD-1 in a fashion similar to the cancer-specific TILs, with the striking distinction of absent CD39 expression. Among lung cancers, the proportion of CD39(-) bystanders was particularly high in EGFR-mutant tumors. This raises the interesting hypothesis that only a specific subset of TILs, such as those expressing CD39, actually influence response to immunotherapy. TBL: A sizeable, heterogeneous population of CD39(-) bystander TILs may be to blame for some of the confusion surrounding variable responses to immunotherapy. | Simoni, Nature 2018