Introduction
Results
hPD-L1 induces clustering of hPD-1 at TCR microclusters
a
SHP2 transiently translocates at hPD-1 microclusters triggered by hPD-1-hPD-L1 binding to suppress T cell activation
a
A Blocking antibody for hPD-1-hPD-L1 binding inhibits hPD-1 microcluster formation and recovers T cell suppression at a sufficient concentration of each antibody
a
Each antibody requires its own optimal concentration for recovering from T cell suppression
a
hPD-L2 possesses the same inhibitory functions as hPD-L1 and is useful to determine the actual effects of ICIs
a
a
A tendency might be found to cancel the PD-1-mediated T cell suppression more effectively with combinational use of anti-hPD-1 and anti-hPD-1 ligands
a
Discussion
In this paper, we evaluated the blocking efficiencies of various anti-hPD-1, anti-hPD-L1, or anti-hPD-L2 against hPD-1-hPD-1 ligand bindings and also their combination by biochemical, physiological, and molecular imaging techniques. To choose the optimal therapies for individual cancer patients, the basic experiments of PD-1, including the molecular imaging in this paper, will become increasingly important and these kinds of studies will be applied to clinical practice in the future.