Manipulation of co-stimulatory or co-inhibitory checkpoint proteins allows for 
the reversal of tumor-induced T-cell anergy observed in cancer. The field has 
gained credence given success with CTLA-4 and PD-1 inhibitors. These molecules 
include immunoglobulin family members and the B7 subfamily as well as the TNF 
receptor family members. PD-L1 inhibitors and LAG-3 inhibitors have progressed 
through clinical trials. Other B7 family members have shown promise in 
preclinical models. TNFR superfamily members have shown variable success in 
preclinical and clinical studies. As clinical investigation in tumor immunology 
gains momentum, the next stage becomes learning how to combine checkpoint 
inhibitors and agonists with each other as well as with traditional 
chemotherapeutic agents.