PD-L1 inhibitors are a class of immunotherapy drugs used to treat various cancers by helping the body’s immune system recognize and attack cancer cells more effectively.

What is PD-L1?

  • PD-L1 (Programmed Death-Ligand 1) is a protein found on the surface of many cells, including some cancer cells.
  • It binds to a receptor called PD-1 on T-cells (a type of immune cell).
  • When PD-L1 binds to PD-1, it sends an “off” signal to the T-cell, preventing it from attacking the cell it’s interacting with.

Why does this matter in cancer?

  • Many cancer cells overexpress PD-L1, using it as a shield to evade immune detection.
  • This allows tumors to grow unchecked by “turning off” T-cells that would normally kill them.

How PD-L1 Inhibitors Work:

PD-L1 inhibitors are monoclonal antibodies that block the interaction between PD-L1 on tumor cells and PD-1 on T-cells.

 Result: T-cells remain active and can recognize and destroy cancer cells.

Examples of PD-L1 Inhibitors:

These drugs typically end in “-lizumab” and are FDA-approved for specific cancers:

  • Atezolizumab (Tecentriq)
  • Durvalumab (Imfinzi)
  • Avelumab (Bavencio)

Related drugs target PD-1 directly (on the T-cell):

  • Nivolumab (Opdivo)
  • Pembrolizumab (Keytruda)

Cancers Treated with PD-L1/PD-1 Inhibitors:

These therapies have been approved or studied for:

  • Non-small cell lung cancer (NSCLC)
  • Melanoma
  • Bladder cancer
  • Triple-negative breast cancer (TNBC)
  • Renal cell carcinoma
  • Head and neck cancers
  • Hodgkin lymphoma
  • Esophageal and gastric cancers
  • Cervical cancer
  • Liver cancer

How Do Clinicians Decide to Use It?

  • PD-L1 expression testing is often performed using immunohistochemistry (IHC).
  • Tumors with high PD-L1 expression are more likely to respond, but responses can still occur in low or negative cases.
  • Tumor mutational burden (TMB) and microsatellite instability (MSI) may also inform decisions.

Benefits and Challenges:

Pros:

  • Can produce durable responses, especially in advanced or metastatic cancer.
  • Generally less toxic than traditional chemotherapy.
  • Can be combined with chemo or targeted therapy for greater efficacy.

Cons:

  • Only a subset of patients respond.
  • Can cause immune-related side effects, such as inflammation of the lungs (pneumonitis), thyroiditis, colitis, or hepatitis.
  • Expensive and not suitable for all cancers or all patients.

Summary:

PD-L1 inhibitors are a powerful tool in modern oncology, especially for tumors that suppress the immune system through PD-L1 overexpression. By blocking this immune checkpoint, these drugs help the body fight cancer more effectively — often resulting in better outcomes and longer survival in select patients.