How Pembrolizumab Works
Pembrolizumab is a humanized monoclonal antibody that blocks the PD-1 receptor on T cells, preventing its interaction with PD-L1 and PD-L2 ligands, thereby releasing the brake on your immune system and allowing it to recognize and attack cancer cells. 1, 2
The Basic Mechanism
Your immune system has built-in checkpoints that normally prevent it from attacking your own body. Cancer cells exploit this system by expressing proteins called PD-L1 and PD-L2 on their surface. When these proteins bind to the PD-1 receptor on your immune cells (T cells), they essentially tell your immune system to "stand down" and leave the cancer alone. 1, 2
Pembrolizumab works by:
Binding directly to the PD-1 receptor on your T cells, physically blocking the interaction between PD-1 and its ligands (PD-L1 and PD-L2). 1, 2
Releasing the inhibition of your immune response that the cancer was causing, which restores your body's natural anti-tumor immunity. 1, 2
Allowing your T cells to proliferate and produce cytokines that help fight the cancer, functions that were previously suppressed by the PD-1 pathway. 2
Why This Matters for Your Cancer
The reason pembrolizumab may work for your specific cancer depends on several factors:
Cancers with high mutation rates (like those with microsatellite instability-high or mismatch repair deficiency) create more abnormal proteins that your immune system can recognize as foreign, making them more responsive to pembrolizumab. 1, 3
Tumors expressing PD-L1 are actively using this checkpoint to hide from your immune system, so blocking PD-1 can be particularly effective. 1, 4
High tumor mutational burden means more potential targets for your immune system to attack once pembrolizumab removes the brake. 1, 4
What to Expect
The response takes time because pembrolizumab doesn't directly kill cancer cells—it enables your immune system to do so. The median time to response is approximately 3 months. 5
Responses can be durable when they occur, with some patients maintaining complete responses for years because your immune system develops memory against the cancer. 6, 3
Initial tumor growth may occur (pseudoprogression) as immune cells infiltrate the tumor before it shrinks, which is why your doctor will carefully assess whether treatment is working. 5
The Immune-Related Side Effects
Because pembrolizumab removes a brake on your immune system, it can sometimes cause your immune system to attack normal tissues, leading to immune-related adverse events such as inflammation of the lungs (pneumonitis), colon (colitis), liver (hepatitis), or endocrine glands (thyroid problems). 1, 4 These occur because the same checkpoint that cancer exploits also helps prevent autoimmunity in healthy tissues. 4