T cell exhaustion: early or late in tumour progression?

Chronic antigen exposure underlies the stepwise acquisition of a terminally dysfunctional state by CD8+ T cells, commonly known as exhaustion, which is considered a major cause of failed cancer immunosurveillance. Recent data from models of viral infection show that the precursors of terminally exhausted T cells emerge early during disease course, prior to continuous signalling through the T cell receptor. I speculate that these findings might indicate that, at least in some settings, T cell exhaustion may emerge as a late consequence — rather than an early determinant — of cancer progression. Recent studies in mouse models of viral infection showed that precursors of terminally exhausted T cells emerge early during the course of disease. Here, Galluzzi discusses these findings and what they may mean for our understanding of tumour immunology and responses to immunotherapy with immune checkpoint blockade.