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.
And one of the major advances that has occurred in the last
few years is the development of checkpoint inhibitor blockade.
Immune checkpoints prevent
ongoing immune responses.
They’re part of the normal immune response
to make sure that it doesn’t get out of hand.
Now if you have an infection, once you’ve cleared the
infection, you need to dampen down the immune response.
But of course with a
tumor it’s always there.
It’s not a transient thing.
Most infections are transient.
Pathogens come, they go, the immune
response gets rid of them and they’re gone.
So you want to down regulate
the immune response.
But of course a tumor
is there all the time.
So you want to get rid of this natural checkpoint
inhibition that occurs in the immune response.
So let’s have a look at how therapeutically
we can use checkpoint inhibitor blockade.
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.
On the surface of the cytotoxic T-lymphocyte is a
molecule called PD-1, stands for programmed death-1.
On the surface of the tumor cell is a ligand
for that molecule, PD-ligand-1 (PD-L1).
This sends a signal into the CD8+
T-cell that prevents its activity.
So there is an inactivation
of the T-cells.
And this PD-L1/PD-1 inhibition of the cytotoxic
T-lymphocyte allows the tumor to grow.
However if one uses a monoclonal
antibody directed to either of these
two interacting molecules, in other
words an antibody against PD-1.
Or alternatively an
antibody against PD-1L.
You can block this inhibition
of the CTL activation.
And therefore the tumor
cells are killed.