FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis

Cancer Cell. 2015 Sep 14;28(3):285-95. doi: 10.1016/j.ccell.2015.08.004.


Immune checkpoint blockade of the programmed cell death protein 1 (PD-1) pathway by monoclonal antibodies (Abs) has shown promising clinical benefit in the treatment of multiple cancer types. We elucidated the contribution of the fragment crystallizable (Fc) domains of anti-PD-1 and anti-PD-ligand 1 (L1) Abs for their optimal anti-tumor activity. We revealed that distinct Fcγ receptor (FcγRs) dependency and mechanisms account for the in vivo activity of anti-PD-1 versus anti-PD-L1 Abs. Anti-PD-1 Abs were found to be FcγR independent in vivo; the presence of FcγR-binding capacity compromises their anti-tumor activity. In contrast, the anti-PD-L1 Abs show augmented anti-tumor activity when activating FcγR binding is introduced into the molecules, altering myeloid subsets within the tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • B7-H1 Antigen / immunology*
  • Cell Line, Tumor
  • Ligands
  • Mice
  • Neoplasms / immunology*
  • Programmed Cell Death 1 Receptor / immunology*
  • Receptors, IgG / immunology*
  • Tumor Microenvironment / immunology


  • Antibodies
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Ligands
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, IgG