What does PD-L1 positive or negative mean?

Abstract

Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti-PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading to constitutive PD-L1 expression on cancer cells or inducible PD-L1 expression on cancer cells and noncancer cells in response to a T cell infiltrate. A tumor may be PD-L1 negative because it has no T cell infiltrate, which may be reversed with an immune response. Finally, a tumor that is unable to express PD-L1 because of a genetic event will always be negative for PD-L1 on cancer cells.

Figure 1.

Examples of different mechanisms leading to PD-L1 positivity or negativity. (a) Constitutive PD-L1 expression but no T cell infiltrate, resulting in constitutive PD-L1 expression in all cancer cells. (b) Constitutive PD-L1 expression with additional inducible expression by a T cell infiltrate, resulting in both constitutive and inducible PD-L1 expression in cancer cells. (c) Adaptive immune resistance, leading to reactive PD-L1 expression induced in cells that are at the site of a CD8⁺ T cell infiltrate. (d) PD-L1–negative tumor caused by absent T cell infiltration. By IHC, a tumor with JAK1/2 loss of function mutations and genetically negative for inducible PD-L1 would look similar without a CD8 T cell infiltrate (because of a lack of chemokine production in response to interferon-γ) and no PD-L1 expression in the tumor.