Table 2.
Approaches for targeting feedback inhibition in the tumor-immune microenvironment
| Target | Examples under clinical investigation ± ICB | References |
|---|---|---|
| Dual checkpoint blockade | Anti-CTLA-4 Anti-TIM3 Anti-LAG3 Anti-TIGIT Anti-VISTA |
Larkin et al., 2015; Postow et al., 2015
Sakuishi et al., 2010; Koyama et al., 2016 Liu et al., 2015; L. Wang et al., 2011 |
| Costimulatory agonist | Anti-GITR Anti-ICOS Anti-OX40 Anti-CD27 |
Sanmamed et al, 2015 |
| Regulatory T cells | Anti-CD25 | Arce Vargas et al., 2017 |
| IDO1 inhibitors | Prendergast et al, 2017 | |
| Epigenetic changes | DNMT inhibitors HDAC inhibitors |
Topper et al, 2017 Ghoneim et al., 2017 |
| Myeloid suppressor cells | CSF1R inhibitor/antibodies PI3Kγ inhibitor Class IIa HDAC inhibitors |
Zhu et al, 2014 |
| De Henau et al., 2016; Kaneda et al., 2016 | ||
| Guerriero et al., 2017 | ||
| Cytokines | JAK inhibitors | Benci et al, 2017 |
| TGFβ inhibitors/antibodies | Tauriello et al, 2018; Mariathasan et al, 2018 | |
| MET inhibitors | Glodde et al, 2017 | |
| Immunometabolism | IDO1 inhibitors A2AR antagonists Arginase inhibitors Glutaminase inhibitors |
Prendergast et al, 2017 Cekic and Linden, 2016 |