%0 Journal Article
%T CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.
%A Lim RJ
%A Salehi-Rad R
%A Tran LM
%A Oh MS
%A Dumitras C
%A Crosson WP
%A Li R
%A Patel TS
%A Man S
%A Yean CE
%A Abascal J
%A Huang Z
%A Ong SL
%A Krysan K
%A Dubinett SM
%A Liu B
%J Cell Rep Med
%V 5
%N 4
%D 2024 Apr 16
%M 38518770
%F 16.988
%R 10.1016/j.xcrm.2024.101479
%X 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.