Preclinical Evidence That PD1 Blockade Cooperates with Cancer Vaccine TEGVAX to Elicit Regression of Established Tumors

Biomarker studies have shown that expression of the T cell co-regulatory ligand PD-L1 on tumor cells correlates with clinical responsiveness to the PD-1 antibody nivolumab. Here we report the findings of a preclinical cancer vaccine study demonstrating a similiar correlate where PD-L1 is upregulated in the tumor microenvironment. We formulated an IFNγ-inducing cancer vaccine called TEGVAX that combined GM-CSF and multiple toll-like receptor agonists to increase the number of activated dendritic cells. Treatment of established tumors with TEGVAX retarded tumor growth in a manner associated with enhanced systemic anti-tumor immunity. Unexpectedly, TEGVAX also upregulated PD-L1 expression in the tumor microenvironment, possibly explaining why tumors were not eliminated completely. In support of this likelihood, PD-L1 upregulation in this setting relied upon IFNγ-expressing tumor-infiltrating CD4+ and CD8+ T cells and administration of a PD-1 blocking antibody with TEGVAX elicited complete regression of established tumors. Taken together, our findings provide a mechanistic rationale to combine IFNγ inducing cancer vaccines with immune checkpoint blockade.