Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8 + T cells
Significance Recent data suggest that patients harboring immunologically incompetent tumors fail to respond to programmed death 1 (PD-1) blockade. We have developed a mouse tumor model that mimics resistance found in human tumors, and we show that intratumoral injections of a high IFN-inducing CpG oligonucleotide, SD-101, can rapidly lead to durable rejection of anti–PD-1 nonresponder tumors and generate systemic immunity to untreated distant-site tumors. The change in tumor microenvironment caused by SD-101 leads to rapid T-cell infiltration and generation of multifunctional CD8 + T cells. These studies provide significant insights into the synergy between PD-1 blockade and local TLR9 activation and provide the experimental support for clinical studies of combination therapy with PD-1 blockade and intratumoral SD-101.