fig5

Figure 5. Drug targets combined with PD-1/PD-L1 inhibitors in clinical trials. (A) Top 20 combination therapy targets across 7,381 clinical trials; (B) PD-1/PD-L1-related bispecific or bifunctional combination antibodies in clinical trials or on the market, with each dot representing one drug; (C) Mechanisms of the most common combination therapy targets. PD-1: Programmed death-1; PD-L1: programmed death-ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; LAG-3: lymphocyte activation gene 3; TIGIT: T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains; TGF-β: transforming growth factor beta; IL: interleukin; TLR: Toll-like receptor; CD: cluster of differentiation; TIM-3: T cell immunoglobulin and mucin domain-containing protein 3; NA: not available; VEGF: vascular endothelial growth factor; PARP: poly (ADP-ribose) polymerase; EGFR: epidermal growth factor receptor; MEK: mitogen-activated protein kinase kinase; HDAC: histone deacetylase; HER2: human epidermal growth factor receptor 2; TROP2: trophoblast cell surface antigen 2; ICOS: inducible T-cell costimulator; CLDN: claudin; OX40: OX40 molecule; ILT4: immunoglobulin-like transcript 4; PD-L2: programmed death-ligand 2; CCL: C-C motif chemokine ligand; GDP: guanosine diphosphate; TKI: tyrosine kinase inhibitor; ERK: extracellular signal-regulated kinase; APC: antigen-presenting cell; MHC: major histocompatibility complex; TCR: T cell receptor; SIRPα: signal regulatory protein alpha; ADO: adenosine; ATP: adenosine triphosphate; Treg: regulatory T; TAM: tumor-associated macrophage; MDSC: myeloid-derived suppressor cell; iDC: immature dendritic cell; mDC: mature dendritic cell.