1. Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2015.173
Figure 4 Activation of antitumour responses by checkpoint-blocking antibodies against PD-1 or PD-L1
Figure 4 | Activation of antitumour responses by checkpoint-blocking antibodies against PD-1 or PD-L1. Upper panel: T-cell activation promotes PD-1 expression by T cells and the secreted IFN-γ induces PD-L1 expression by the target cell. Binding of PD-1 to PD-L1 blocks TCR signalling and induces T-cell exhaustion. Anti-PD-1 or anti-PD-L1-blocking antibodies reinvigorate T cells and restore their cytolytic functions (mediated by the release of soluble factors and by ligands of death receptors FasL and TRAIL). Lower panel:hypoxic conditions and proinflammatory cytokines promote the expression of PD-L1 both by tumour cells and MDSCs and of PD-1 by TAMs, which release IL-10 upon PD-1–PD-L1 interaction. Anti-PD-1 or anti-PD-L1-blocking mAbs revert T-cell exhaustion and attenuate the immunosuppressive intratumour environment. Abbreviations: ADCC, antibody-dependent direct cytotoxicity; APC, antigen-presenting cell; CD40L, CD40 ligand; CTL, cytotoxic T lymphocyte; CTLA-4, cytotoxic T-lymphocyte protein 4; FasL, tumour necrosis factor ligand superfamily member 6; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; PD-1, programmed cell death protein 1; PD-L1, programmed cell death 1 ligand 1; TCR, T-cell receptor; TRAIL, tumour necrosis factor ligand superfamily member 10; TRAILR, tumor necrosis factor receptor superfamily member 10; TREG cell, regulatory T cell.
Prieto, J. et al. (2015) Immunological landscape and immunotherapy of hepatocellular carcinoma
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