TNF and neoplasm: Mechanistically, PD-1 blockade reinvigorates exhausted CD8+/CD4+ T cells, enhancing proliferation, IFN-γ/TNF-α production, and perforin/granzyme-mediated cytolysis; additional effects include improved NK activity, revitalized tumor-draining node responses, and modulation of myeloid cells, with a possible, but generally outweighed, expansion of PD-1+ Tregs (Figure 4) [96].