Antitumor therapeutic vaccination induces immunosuppressive dendritic cells

Vaccination induces immunostimulatory signals which are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Thus, here we characterized IL-10-producing cells treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1. These IL-10+ DC showed impaired in vitro T-cell stimulatory capacity, which was rescued by incubation with IL-10R and PD-L1-inhibiting antibodies.

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Llopiz D, Ruiz M, Infante S, Villanueva L, Silva L, Hervas-Stubbs S, Alignani D, Guruceaga E, Lasarte JJ, Sarobe P