Four different hypothetical models are presented, along with the sites in which PD‑L1
might be active, either in tumor or TDLN. (A) The traditional model, in
which PD‑L1 is expressed on the tumor cell itself and directly inhibits killing of the
target cell by activated PD‑1+ effector T cells. (B) Model in
which inhibitory PD‑L1 is expressed on DCs during the initial priming of naive
tumor-specific T cells. (C) Indirect model in which PD‑L1 delivers an
activating signal to Tregs via PD‑1 and the activated Tregs then mediate immune
suppression. (D) Model in which DCs in tumor or TDLNs constantly interact
with mature, exhausted effector T cells and PD‑L1 serves to inhibit reactivation driven
by B7-CD28 costimulation. In the figure, PD‑L1 is depicted as being expressed on the
same DC that could reactivate the exhausted T cell, but this interaction might also
occur in trans (PD‑L1 might be expressed on a neighboring macrophage or other APC).