PD-L1, PD-1, TMB and Lung Cancer

Immunotherapy is a type of therapy in which the immune system, the patient's own immune system, is harnessed to target their tumor cells and attack their tumor cells.

The most commonly used of these are drugs that block the interaction between PD-1 and PD-L1. PD-1 is generally on the surface of immune cells, whereas PD-L1 has a broader presence, including on the surface of tumor cells.

The interaction between PD-1 and PD-L1 is anticipated to be an important part of the effect of these immune checkpoint inhibitors. The idea of these drugs is to block this interaction, which is typically a negative interaction for the immune system. By blocking this negative interaction, the immune system is stimulated to attack the tumor cells.

In my own practice, I generally use single-agent pembrolizumab, although, again, there may be additional options that receive approval in the coming months.

In patients who have particularly high PD-L1 expression, for instance, PD-L1 expressed in at least half of their tumor cells, I may use single-agent pembrolizumab.

On the other hand, in patients who have positive but lesser amounts of staining for PD-L1, or patients who do not have any PD-L1 expression, in general, I have combined chemotherapy with a PD-1 or PD-L1 inhibitor.

It is important for patients to recognize that even patients who do have no expression of PD-L1 can have a response to a PD-1 or PD-L1 inhibitor.

Also, there appears to be very significant benefit from adding a PD-1 or PD-L1 inhibitor to chemotherapy, even in patients who have low or no expression of PD-L1.

"What is tumor mutation burden?"

Now, there's a tremendous amount of work that is going on looking at various biomarkers, markers that predict the likelihood of one benefiting from immunotherapy.

The one that is the furthest along is something called tumor mutation burden.

If you remember back to biology, DNA, which is what we refer to as our genes, makes RNA, which then makes a protein. So, a mutation at the level of the DNA has the potential to make an abnormal protein.

Our sense is that the immune system should only be able to react against cells that are displaying these abnormal proteins. This led to the idea that having a higher number of these mutations is associated with a greater likelihood of benefit from PD-1 or PD-L1 inhibitors when used as a single agent.

The answer is now quite clear. Tumor mutation burden also can predict who is more likely to respond to immunotherapy and who is more likely to have disease controlled with immunotherapy.

One way of looking at this is to look at the tumor cells themselves, but our ability to look at results in blood cells has increased quite a bit. Now, there are also tests that look for the number of mutations, the tumor mutation burden, in the blood.