Programmed cell death protein ligand 1 (PD-L1) interferes with anticancer immune response by binding programmed PD-1 and B7.1 (CD80), negative regulators of T-cell activation. In a study reported in Nature, Herbst and colleagues showed that treatment with an anti–PD-L1 antibody (MPDL3280A) produced responses across multiple cancer types in patients with tumors expressing high levels of PD-L1 and particularly when PD-L1 was expressed by tumor-infiltrating immune cells. Responses were also associated with T-helper type 1 gene expression, CTLA-4 (cytotoxic T-lymphocyte–associated protein-4) expression, and absence of fractalkine (CX3CL1) in baseline tumor samples.
The investigators concluded: “[T]hese data suggest that MPDL3280A is most effective in patients in which preexisting immunity is suppressed by PD-L1 and is reinvigorated on antibody treatment.”
More detailed information about this study may be found on page 48 in this issue of The ASCO Post. ■
Herbst RS, et al: Nature 515:563-567, 2014.