Understanding a tumor’s characteristics is a standard part of modern lung cancer treatment. Among these, the status of a protein known as PD-L1 has emerged as a significant factor for guiding therapy. Learning about PD-L1 expression provides valuable insights into how a lung tumor might interact with the body’s immune system. This information helps doctors tailor treatment strategies to each patient for more effective, personalized care.
The Role of PD-L1 in the Immune System
The body’s immune system contains specialized cells, called T-cells, which are designed to identify and eliminate foreign invaders and abnormal cells, including cancer. To prevent these T-cells from attacking healthy tissues, the body employs a natural “brake” system, often referred to as an immune checkpoint. A prominent part of this system involves two proteins: PD-1, located on the surface of T-cells, and PD-L1, found on various other cells throughout the body.
When PD-1 on a T-cell connects with PD-L1 on a healthy cell, it signals the T-cell to stand down, preventing an immune attack. This interaction acts like a “key” (PD-1) fitting into a “lock” (PD-L1), turning off the T-cell’s attack.
Unfortunately, some lung cancer cells exploit this natural protective mechanism. These cancer cells produce high amounts of PD-L1 on their surface, essentially displaying a “don’t attack me” signal to the immune system.
By overexpressing PD-L1, lung cancer cells evade detection and destruction by T-cells, allowing the tumor to grow and spread. Understanding this immune evasion mechanism paved the way for new cancer treatments.
Testing for PD-L1 Expression
Determining the level of PD-L1 expression in lung cancer involves a precise diagnostic process. This measurement is performed on a tumor tissue sample obtained through a biopsy.
After a tissue sample is acquired, it is sent to a laboratory for immunohistochemistry (IHC). IHC uses specific antibodies that are designed to bind only to the PD-L1 protein. These antibodies contain a detectable marker, which “stains” the PD-L1 proteins present on the cancer cells, making them visible when viewed under a microscope. Pathologists then analyze the stained tissue to quantify the amount of PD-L1 expressed by the tumor cells. A minimum of 100 viable tumor cells on the stained slide is usually required for an adequate evaluation.
Interpreting PD-L1 Test Results
The results of PD-L1 testing in lung cancer are primarily reported using a metric called the Tumor Proportion Score (TPS). The TPS represents the percentage of viable tumor cells that show partial or complete staining for PD-L1 on their cell membranes, regardless of the intensity of the stain.
Pathologists categorize TPS into common ranges to guide clinical decisions. A TPS of less than 1% indicates negative or very low PD-L1 expression, suggesting minimal reliance on this specific immune evasion pathway. Low expression is defined as a TPS ranging from 1% to 49%, indicating a moderate number of tumor cells display PD-L1. High expression is characterized by a TPS of 50% or greater, indicating that a significant proportion of the tumor cells are utilizing PD-L1 to hide from the immune system. These categories help predict how the tumor might respond to certain immune-modulating treatments.
How PD-L1 Status Guides Lung Cancer Treatment
The PD-L1 status of a lung tumor influences treatment strategies, particularly those involving immunotherapy. For patients with a high PD-L1 expression, defined as a Tumor Proportion Score (TPS) of 50% or greater, immunotherapy with a PD-1 or PD-L1 inhibitor is often a first-line, standalone treatment. These medications, such as pembrolizumab, atezolizumab, and cemiplimab, are designed to “release the brakes” on the immune system by blocking the interaction between PD-1 and PD-L1. This blockade allows T-cells to recognize and attack cancer cells more effectively.
For patients with lower PD-L1 expression, specifically a TPS between 1% and 49%, immunotherapy is still an option but is frequently administered in combination with chemotherapy. This combined approach aims to enhance the immune response while also directly targeting the cancer cells with chemotherapy. Even for tumors with negative PD-L1 expression (TPS less than 1%), immunotherapy, often in combination with chemotherapy, may still be considered.
PD-1 inhibitors block the PD-1 protein on the T-cells, while PD-L1 inhibitors target the PD-L1 protein on the tumor cells. Both types of inhibitors aim to disrupt the same immune checkpoint pathway, allowing the immune system to reactivate its anti-cancer activity. The specific choice of medication and regimen depends on the patient’s PD-L1 score, overall health, and other tumor characteristics.