Tumor Evasion of the Immune Response and Immune Checkpoint Blockade

00:01 It’s quite an exciting time in tumor immunology at this moment because we are beginning to be able to really harness the full power of the immune system to fight tumor cells.

00:16 And one of the major advances that has occurred in the last few years is the development of checkpoint inhibitor blockade.

00:27 Immune checkpoints prevent ongoing immune responses.

00:32 They’re part of the normal immune response to make sure that it doesn’t get out of hand.

00:37 Now if you have an infection, once you’ve cleared the infection, you need to dampen down the immune response.

00:42 But of course with a tumor it’s always there.

00:44 It’s not a transient thing.

00:47 Most infections are transient.

00:50 Pathogens come, they go, the immune response gets rid of them and they’re gone.

00:53 So you want to down regulate the immune response.

00:56 But of course a tumor is there all the time.

01:00 So you want to get rid of this natural checkpoint inhibition that occurs in the immune response.

01:12 So let’s have a look at how therapeutically we can use checkpoint inhibitor blockade.

01:20 Here we have a cytotoxic T- lymphocyte, and it is recognizing a peptide from the tumor being presented to its T-cell receptor by MHC.

01:33 On the surface of the cytotoxic T-lymphocyte is a molecule called PD-1, stands for programmed death-1.

01:43 On the surface of the tumor cell is a ligand for that molecule, PD-ligand-1 (PD-L1).

01:52 This sends a signal into the CD8+ T-cell that prevents its activity.

02:01 So there is an inactivation of the T-cells.

02:05 And this PD-L1/PD-1 inhibition of the cytotoxic T-lymphocyte allows the tumor to grow.

02:14 However if one uses a monoclonal antibody directed to either of these two interacting molecules, in other words an antibody against PD-1.

02:24 Or alternatively an antibody against PD-1L.

02:29 You can block this inhibition of the CTL activation.

02:35 And therefore the tumor cells are killed.