CXCL9/10-engineered dendritic cells promote T cell activation and enhances immune checkpoint blockade for lung cancer.

Immune checkpoint blockade (ICB), notably Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) inhibition, has revolutionized the treatment of non-small cell lung cancer (NSCLC). However, durable responses are only observed in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment can lead to deficient T-cell recruitment and ICB resistance. We evaluated in situ vaccination with CXCL9 and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a novel strategy to overcome resistance to ICB using Lkb1-null murine NSCLC model. We utilized single-cell RNA-seq to evaluate alterations of immune infiltration associated with the new therapy, which combines intratumoral CXCL9/10-DC administration and PD-1 inhibition. Overall design: Murine tumors were harvested on day 14 following subcutaneous inoculation with KPL-3M tumor cells and treatment. Single-cell suspension of murine tumors was stained with Zombie-NIR LIVE/DEAD stain and CD45 antibody before being isolated for alive CD45+ cells by Fluorescence-activated cell sorting (FACS) with a 100-mm nozzle.