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Vaccination induces immunostimulatory signals that are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Here we characterized IL-10-producing cells in different tumor models 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. In vivo IL-10 blockade during vaccination decreased the proportion of IL-10+ DC and improved their maturation, without modifying PD-L1 expression. Similarly, PD-L1 blockade did not affect IL- 10 expression. Interestingly, vaccination combined with simultaneous blockade of IL-10 and PD-L1 induced stronger immune responses, resulting in a higher therapeutic efficacy in tumor-bearing mice. These results show that vaccine-induced immunoregulatory IL- 10+ DC impair priming of antitumor immunity, suggesting that therapeutic vaccination protocols may benefit from combined targeting of inhibitory molecules expressed by this DC subset.

Los asilos de ancianos son instituciones con una alta prevalencia de infecciones del tracto urinario ocasionado por Escherichia coli productoras de ß-lactamasas de espectro extendido (BLEE), con diversos factores de virulencia. El objetivo del estudio fue determinar la frecuencia del gen blaCTX-M y de ocho genes de virulencia en 35 E. coli uropatógenas productoras de BLEE provenientes de seis asilos en Perú, durante el 2018. El 57,1% (20/35) de las E. coli fueron portadores del gen blaCTX-M. Además, se obtuvo una frecuencia del 46% (15/35) y 37% (13/35) de hly-alfa y cnf-1, respectivamente; elevada presencia de los genes iucC (63%, 22/35), aer (94%, 33/35) y chuA (94%, 33/34) y una frecuencia del 46% (16/35) y del 91% (32/34) de los genes pap GII y nanA, respectivamente. Existe predominancia en la distribución del gen blaCTX-M, además de una alta frecuencia de exotoxinas que le confieren una ventaja competitiva para diseminarse hacia el torrente sanguíneo.

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