Exhausted T cells are characterized as a fraction of tumor-reactive CD8+ T cells that are unable to lyse tumor cells, and have impaired effector functions including production of potent effector cytokines (e.g., TNFα, IFNγ, IL-2) together with high expression of co-inhibitory receptors including CTLA-4, PD-1, TIM-3, TIGIT or LAG-3.13,21,22,145 More recently, there has been an increasing focus on the transcriptional regulators that initiate, amplify or maintain the exhaustion state. Here, TNF is linked to neoplasm.