Lung cancer is a leading cause of cancer-related deaths worldwide, characterized by the uncontrolled growth of abnormal cells in the lungs. The body’s immune system is equipped with specialized cells that identify and eliminate threats, including cancerous cells. Normally, this system can distinguish between healthy and harmful cells.
However, some cancer cells develop strategies to go unnoticed by these defenses, an ability known as immune evasion. Understanding the mechanisms that allow lung cancer cells to hide from the body’s protectors helps reveal how the disease progresses and identifies potential targets for treatment.
The Role of the PD-L1 Protein
Programmed death-ligand 1, or PD-L1, is a protein found on the surface of various cells. In a healthy individual, PD-L1 helps maintain immune balance by preventing the immune system from attacking the body’s own tissues. It functions as an “off-switch” by binding to its receptor, PD-1, which is present on activated T-cells—the immune system’s primary soldiers. This interaction signals to the T-cell that the cell it has encountered is friendly, preventing an autoimmune reaction.
Some lung cancer cells co-opt this natural mechanism for their own survival. These tumors can express high levels of PD-L1 on their surface, effectively disguising themselves as healthy tissue. When a T-cell encounters a cancer cell with abundant PD-L1, the binding delivers an inhibitory signal that deactivates the T-cell. This prevents it from recognizing the cancer cell as a threat and allows the tumor to grow without interference from the immune system.
Measuring PD-L1 Expression Levels
To determine if a lung tumor is using the PD-L1 pathway, clinicians measure its expression levels from a tumor sample obtained through a biopsy. The tissue is analyzed in a lab using a technique called immunohistochemistry (IHC), which uses specialized antibodies to bind to the PD-L1 protein and make it visible.
The results are quantified using the Tumor Proportion Score (TPS). The TPS represents the percentage of tumor cells in the sample that show PD-L1 staining on their surface.
Based on the TPS, a patient’s lung cancer is categorized into one of three groups. A TPS of less than 1% is considered low or negative expression. A score between 1% and 49% is categorized as intermediate expression. A TPS of 50% or greater is classified as high expression.
How PD-L1 Levels Impact Survival
The level of PD-L1 expression on lung cancer cells is a predictive biomarker, offering insight into a patient’s prognosis and treatment path. While a high PD-L1 presence was once viewed as a negative characteristic, this perspective has shifted. Today, a high PD-L1 score indicates that a patient is likely to respond favorably to a specific class of treatments.
The PD-L1 level itself does not directly determine survival but instead predicts the probable effectiveness of immunotherapy. For patients with non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer cases, a high PD-L1 expression (TPS ≥50%) is associated with better outcomes when treated with immune checkpoint inhibitors.
Studies show that patients with high PD-L1 levels who receive this immunotherapy often experience improved progression-free and overall survival compared to those treated with chemotherapy alone. The PD-L1 score helps oncologists identify which patients are the best candidates for these treatments, enabling a more personalized approach to care.
Immunotherapy as a Targeted Treatment
The discovery of the PD-L1 pathway’s role in cancer evasion led to the development of drugs known as immune checkpoint inhibitors. These therapies are a form of immunotherapy that leverages the body’s own immune system to fight cancer. The drugs work by disrupting the interaction between the PD-L1 protein on tumor cells and the PD-1 receptor on T-cells.
By blocking either PD-L1 or PD-1, these inhibitor drugs prevent the deactivation of T-cells. This action releases the “brakes” on the immune response, allowing T-cells to recognize the cancer cells as foreign and mount an attack.
Several immune checkpoint inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for treating lung cancer, particularly NSCLC. Drugs like pembrolizumab, atezolizumab, and nivolumab are now commonly used. A patient’s PD-L1 expression level guides when and how these drugs are administered.
For instance, patients with high PD-L1 expression (TPS ≥50%) may be eligible to receive an immune checkpoint inhibitor as a first-line treatment, either alone or with chemotherapy. This targeted strategy has improved outcomes for many individuals with lung cancer.