TNF and neoplasm: These exhausted CD8+ T cells express co-inhibitory molecules (e.g., PD-1, LAG-3, TIM-3, TIGIT) and lose the ability to produce multiple cytokines such as interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2, namely they lose anti-tumor activities [32–35].