PDL1negative

PDL1negative refers to the absence or below-threshold expression of programmed death-ligand 1 (PD-L1) detected on tumor cells and/or tumor-associated immune cells by immunohistochemistry (IHC). PD-L1 is a protein that can be expressed by cancer cells and immune cells in the tumor microenvironment and can interact with the PD-1 receptor on T cells to downplay immune responses. The term is used in oncology to describe tumors that do not meet the cutoffs set by specific PD-L1 testing assays.

PD-L1 testing and scoring methods vary by cancer type and assay. Common PD-L1 IHC assays include 22C3, 28-8, SP263, and SP142, with scoring schemes such as tumor proportion score (TPS), which measures PD-L1 expression on tumor cells, and combined positive score (CPS), which also accounts for PD-L1 on immune cells. Cutoffs for what constitutes “positive” status differ across tests and indications; thresholds such as TPS ≥1% or CPS ≥1 are used in some settings, while higher thresholds may apply in others. Because of assay diversity and tumor heterogeneity, PD-L1 results are context-dependent and should be interpreted within the specific clinical and assay framework.

Clinically, PD-L1 negative status is generally associated with lower response rates to PD-1/PD-L1 inhibitors in several cancers, but it is not an absolute predictor of nonresponse. Some patients with PD-L1 negative tumors can still respond, and responses may be influenced by other factors such as tumor mutational burden, microsatellite instability, prior therapies, and overall patient health. PD-L1 testing often informs treatment decisions alongside other biomarkers and clinical factors, but it is not the sole determinant of therapy choice.

Limitations include intratumoral heterogeneity, sampling variability, and differences among assays that can lead to discordant results. Pre-analytic variables, timing of biopsy, and dynamic changes in PD-L1 expression also affect interpretation.