T cell cross-priming by PD-L1(+) type 1 conventional dendritic cells mediates the antitumor efficacy of a PD-L1×4-1BB bispecific antibody.

PD-L1×4-1BB antitumor efficacy in Batf3+/+ mice depends on type 1 conventional dendritic cells (cDC1s), with PD-L1 on cDC1s and cross-presentation enabling tumor control.

• Why it matters: The work addresses why a PD-L1×4-1BB bispecific antibody performs clinically, despite limited dependence on PD-L1 on malignant cells, and identifies the immune mechanism sustaining activity.
• What they did: In mice, the authors tested PD-L1×4-1BB with Batf3−/− and cDC1 depletion, then measured CD8+ T cell proliferation and cDC1 licensing requirements involving cross-presentation, IL-12, 4-1BB costimulation, and CD40L.
• The result: PD-L1×4-1BB increased cDC1–T cell contacts and activated T cell transcriptional programs, yielding greater cDC1 and activated CD8+ T cell infiltration and improved tumor control, further enhanced by Flt3L-driven dendritic-cell abundance.