The PD-L1 SP142 assay is a diagnostic test designed to measure the presence of Programmed Death-Ligand 1 (PD-L1) protein in cancer tissue. PD-L1 is a protein found on the surface of tumor cells and immune cells within the tumor environment. The SP142 test uses a specific antibody clone to detect this protein’s expression levels. This diagnostic information determines a patient’s eligibility for certain modern cancer immunotherapies, guiding oncologists in selecting a targeted treatment approach.
The Role of the PD-L1/PD-1 Axis in Cancer
The immune system uses checks and balances to prevent attacking healthy cells (immune tolerance). A major component of this system is the Programmed Death-1 (PD-1) receptor, which acts like an “off switch” on the surface of T-cells, the primary immune cells responsible for killing cancer. When activated, the PD-1 receptor inhibits the T-cell, effectively putting a brake on the immune response.
Cancer cells exploit this natural regulatory mechanism by expressing the protein PD-L1 on their surfaces. When PD-L1 on a tumor cell binds to the PD-1 receptor on a T-cell, it engages the immune brake, protecting the cancer cell from destruction. This interaction allows the tumor to hide from the host’s immune surveillance and continue to grow.
The PD-1/PD-L1 axis is a primary pathway for cancer immune evasion. Immunotherapy drugs, known as checkpoint inhibitors, are designed to block this interaction, releasing the brakes on the T-cells. By blocking the PD-1/PD-L1 connection, these drugs re-activate the T-cells, allowing them to recognize and attack the cancer. Measuring PD-L1 expression is important because a higher presence of this protein suggests the tumor is actively using this pathway, making it a stronger candidate for targeted treatment.
How the SP142 Assay Identifies PD-L1
The SP142 assay is a specific immunohistochemistry (IHC) test that uses the rabbit monoclonal antibody clone, SP142, to identify PD-L1 protein in a tissue sample. This procedure involves taking a formalin-fixed, paraffin-embedded tissue sample from the patient’s tumor and applying the SP142 antibody. The antibody binds specifically to the PD-L1 protein, and a subsequent chemical reaction creates a visible brown stain where the protein is present.
The SP142 assay focuses on the tumor microenvironment. It evaluates PD-L1 expression on two distinct cell populations: the Tumor Cells (TC) and the Tumor-Infiltrating Immune Cells (IC) present in and around the tumor. This dual assessment provides a comprehensive view of the immune interaction at the tumor site. The test was the first approved by the FDA with an immune cell scoring algorithm, enhancing the visual contrast of immune cell staining.
Different PD-L1 antibody clones, such as 22C3 or 28-8, exist and are associated with different immunotherapy drugs. The SP142 clone is specifically co-developed as a companion diagnostic for the drug atezolizumab (Tecentriq). Because of variations in how each clone binds to PD-L1 and the specific scoring methodology used, the results from the SP142 test are not directly interchangeable with those from other assays. Selecting the correct assay for a specific drug is necessary.
Decoding SP142 Scoring and Interpretation
Interpretation of the SP142 assay involves a pathologist calculating two separate percentages from the stained tissue sample: the Tumor Cell (TC) score and the Immune Cell (IC) score. The TC score represents the percentage of viable tumor cells showing membrane staining for PD-L1. The IC score is the proportion of the total tumor area occupied by PD-L1 expressing immune cells.
The scoring algorithm for the SP142 test is indication-specific, meaning the threshold for a positive result changes depending on the type of cancer being tested. For many indications, the IC score is the primary or sole metric used for decision-making. For example, in triple-negative breast cancer (TNBC), the result is considered positive if the IC score is \(\ge\) 1%.
In other cancers, such as non-small cell lung cancer (NSCLC), a stepwise approach considers both scores. A result might be considered high-positive if \(\ge\) 50% of the TC stain positive or if \(\ge\) 10% of the IC stain positive. If the TC staining is below the threshold, the pathologist evaluates the IC staining, which often includes immune cells like lymphocytes and macrophages within the tumor and its surrounding stroma. These precise percentage thresholds are defined based on clinical trial data showing which patient groups benefit most from the associated immunotherapy drug.
Treatment Decisions Guided by SP142 Results
The SP142 assay serves as a companion diagnostic, linking a patient’s PD-L1 status directly to the use of the anti-PD-L1 immunotherapy drug, atezolizumab (Tecentriq). The specific score dictates whether a patient is eligible for treatment with this medication for certain cancer types. This clinical application transforms the laboratory result into a guide for personalized medicine.
The SP142 assay is a required biomarker test for atezolizumab treatment in several major cancer indications. For patients with metastatic triple-negative breast cancer (TNBC), a positive result is defined by an IC score of \(\ge\) 1%, which indicates eligibility for atezolizumab in combination with chemotherapy. In the context of urothelial carcinoma (bladder cancer), a patient may be identified for treatment if they have an IC score of \(\ge\) 5%.
Specific score thresholds also apply to non-small cell lung cancer (NSCLC), where eligibility criteria vary depending on the treatment setting. For example, a result of \(\ge\) 50% TC or \(\ge\) 10% IC may identify patients who experience enhanced overall survival from atezolizumab treatment. These precise, indication-specific scoring cutoffs confirm the necessity of using the SP142 assay when considering atezolizumab, as clinical evidence is tied directly to these results.