- Lim, Raymond J;
- Salehi-Rad, Ramin;
- Tran, Linh M;
- Oh, Michael S;
- Dumitras, Camelia;
- Crosson, William P;
- Li, Rui;
- Patel, Tejas S;
- Man, Samantha;
- Yean, Cara E;
- Abascal, Jensen;
- Huang, ZiLing;
- Ong, Stephanie L;
- Krysan, Kostyantyn;
- Dubinett, Steven M;
- Liu, Bin
Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance. We evaluate intratumoral (IT) vaccination with CXCL9- and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a strategy to overcome resistance. IT CXCL9/10-DC leads to enhanced T cell infiltration and activation in the TME and tumor inhibition in murine NSCLC models. The antitumor efficacy of IT CXCL9/10-DC is dependent on CD4+ and CD8+ T cells, as well as CXCR3-dependent T cell trafficking from the lymph node. IT CXCL9/10-DC, in combination with ICB, overcomes resistance and establishes systemic tumor-specific immunity in murine models. These studies provide a mechanistic understanding of CXCL9/10-DC-mediated host immune activation and support clinical translation of IT CXCL9/10-DC to augment ICB efficacy in NSCLC.