I'm not sure what are you trying to have answered.

First, for PD-L1 and PD-1 immunotherapy, is to make sure that the marker is overexpressed in the patient for it to work. And just to make sure you understand that almost ALL immunotherapy with biologics is usually "blocking" antibodies. This means that the antibodies prevent activation of the target ad/or the target's ligand.

As for WHY it works... PD-1 and PD-L1 are part of the ever growing complicated T cell activation mechanisms. Specifically, ligation of PD-1 and PD-L1 has shown to inhibit T cell activation. The idea is that in tumors that over express PD-1 and/or PD-L1, it has set up a microenvironment that is shutting down any T cells that can activate against the tumor cells. So... if you block this pathway, you can lead to more T cell activation and thus eridication of the tumor.

This is the simpliest answer I can give.

Antibody-based checkpoint blockade therapies (CTLA-4, PD-1, PD-L1) work by enhancing the cytolytic capacity of CD8 T cells. CD8 T cells are particularly well-suited for treating metastatic malignancies, as they systemically traffic and exhibit antigen-restricted cytotoxicity. In contrast, the non-specific cytotoxicity of conventional chemo- and radiotherapies make them poor candidates for treating metastatic tumors.

Anti-CTLA-4 therapy was the first to receive clinical approval, but had some severe side effects associated with it. Anti-PD-1 therapy was approved that was also effective but had less side effects. Anti-PD-L1 therapy also has less severe side effects relative to anti-CTLA-4 therapy. Each antibody can be administered alone or in combinations to enhance their mechanism, and side effects may be better managed as we learn more about their clinical use (they're still relatively new therapies).

The major advantage of each of these interventions is that they don't require additional patient-specific modifications (they're non-personalized interventions). The same therapy also works in several types to tumors as the immune system acts as the common denominator.

The mechanism for each of these interventions is primarily mediated by their ability to block negative signaling through their respective pathways. Less impactful mechanisms include humoral immune responses against antibody-coated tumors/exhausted T cells and decreased activation thresholds for naive T cells.

Brett P Gross thanks for your answer. I have one more question. Well my opinion is that the methods can be good for the effectiveness or what you are targeting for. Let me ask one more advise from you sir. PD-L1 treatment is cancer cell targeting which means it only controls cancer cell (indirectly controls T cells). So if I want to do the tumor target delivery, then PD-L1 is going to be my main issue.

Do you know any other method that goes to the tumor and initiate the treatment like PD-L1 ?

Thank you for your answer sir.

Shen-An Hwang Thank you for the answer sir.

Brett P Gross sir, I have one more questions following your answer.

" The major advantage of each of these interventions is that they don't require additional patient-specific modifications (they're non-personalized interventions). The same therapy also works in several types to tumors as the immune system acts as the common denominator. "

Does this mean that the Immune checkpoint inhibitors can treat pretty much all tumors ? (well, they may work better for specific kind of cancer but..)

Thanks

Mostly, these therapies delay negative feedback signaling (a safeguard against immunopathology) in all antigen-experienced T cells in a non-antigen-specific manner. They are much less effective in tumors that don't express their targets (e.g., PD-L1) as Shen has correctly mentioned above. Assuming the targets are expressed they theoretically would attack any tumor type to varying extents.

I recommend these papers:

• https://www.ncbi.nlm.nih.gov/pubmed/29228642

• Article PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the An...