Newer (Safer?) Checkpoints: PD-L1 & TIGIT

The programmed cell death 1 (PD-1) protein is a critical regulator of T-cell activation and is also an important therapeutic target for autoimmune diseases. Little is…
ncbi.nlm.nih.gov

Soluble PD-1 are the native equivalent of synthetic monoclonal anti-PD-L1, several of which are currently undergoing cancer trials as checkpoint inhibitors: Roche’s Atezolizumab, AZ’s Durvalumab, Merck’s Avelumab.

Immune cells in diseases like RA overproduce sPD-1, which binds PD-L1 on other immune cells, thereby blocking the latter’s ligation of PD-1 on T-cells to wind down the inflammation. sPD-1 can therefore also serve as a marker of autoimmune disease activity.

Use of anti-PD-L1 in cancer immunotherapy follows the same logic: it keeps alive the activated T-cells to fight the cancer. Measuring the levels of natural anti-PD-L1 antibodies may also serve to gauge tumour burden or the susceptibility of the tumour to PD-1/PD-L1 directed immunotherapy.


Prospects for Targeting PD-1 and PD-L1 in Various Tumor Types

In this review, we will discuss the current status of several anti–PD-1 and anti–PD-L1 antibodies in…
cancernetwork.com


Department of Immunobiology, Dermatology, Medicine and Cancer Immunology Program, Yale Cancer…
jci.org

PD-L1 inhibition may theoretically be safer than inhibiting CTLA4 or PD-1, with less broad-based T-cell activation causing autoimmune phenomena. This is because it does not block ligation of PD-1 by PD-L2, which is expressed only by (self-)antigen-presenting macrophages and dendritic cells to downregulate potential autoimmunity.


TIGIT: A Key Inhibitor of the Cancer Immunity Cycle

Immunotherapies that harness the activity of the immune system against tumors are proving to be an effective therapeutic approach in multiple malignancies. Indeed, through accumulation of genetic mutations, many tumors express antigens that can potentially elicit specific tumor immunity. However, tu…
cell.com