See my post at Ipi Update  empen on 9/28.2011

 Great Question!!!!! 

Ipi works on the surface molecule CTLA-4 which are upregulated during T-cell activation. Most T-cells including the Tregs will have this receptor on their surface. When this receptor is engaged, the immune response is down-regulated.. terminated. So by blocking this receptor with Yervoy (Ipi), the checkpoint remains active.

Anti- PD-1 blocks another receptor called PD-1. It also is up-regulated on the T-cell. Now on the tumor cells, there are receptors called PD-L1. This PD-L1 receptor can bind/engage with PD-1 on the T-cells. When this happens, the immune rsponse is down-regulated and no response is generated.

There is data coming that anti-PD-1  blocks global inhibtion of the T-cells and shows a better response. How much better, still waiting on the data.

warm regards,

Jimmy B

See my post at Ipi Update  empen on 9/28.2011

 Great Question!!!!! 

Ipi works on the surface molecule CTLA-4 which are upregulated during T-cell activation. Most T-cells including the Tregs will have this receptor on their surface. When this receptor is engaged, the immune response is down-regulated.. terminated. So by blocking this receptor with Yervoy (Ipi), the checkpoint remains active.

Anti- PD-1 blocks another receptor called PD-1. It also is up-regulated on the T-cell. Now on the tumor cells, there are receptors called PD-L1. This PD-L1 receptor can bind/engage with PD-1 on the T-cells. When this happens, the immune rsponse is down-regulated and no response is generated.

There is data coming that anti-PD-1  blocks global inhibtion of the T-cells and shows a better response. How much better, still waiting on the data.

warm regards,

Jimmy B

PD-L1 expressed on tumor cells protects them from direct immune attack by the specific (CTL) Cytotoxic T lymphocytes at the effector level at least in vitro, and enhances the tumorigenicity in vivo.  

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade

PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation. The STAT-5 signaling drives the Th2 and Treg phonotype.

So what is left is the Th1 and the Th17 phenotype.

PD-L1 expressed on tumor cells protects them from direct immune attack by the specific (CTL) Cytotoxic T lymphocytes at the effector level at least in vitro, and enhances the tumorigenicity in vivo.  

Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade

PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation. The STAT-5 signaling drives the Th2 and Treg phonotype.

So what is left is the Th1 and the Th17 phenotype.