Blocking of PD-L1 on therapeutic dendritic cells modulate in vitro T cells proliferation and differentiation to Th1 and Th17 subpopulations (P4230)

Abstract

Abstract DCs constitute a promising treatment against melanoma. Recently, we showed the effectiveness of an allogeneic melanoma lysate DC-based immunotherapy for improving long-term survival in melanoma patients. Moreover, an elevated proportion of regulatory T lymphocytes (Tregs) was observed in non-responder patients. PD-L1 is an important co-inhibitory molecule expressed on DCs binding to PD-1 on T cells. This interaction promotes the induction, conversion and maintenance of Tregs, suggesting a role in immunosuppression. Here, we studied if the blockade of PD-1-PD-L1 interaction reverses Tregs differentiation and increases T helper populations. Monocyte-DCs were generated in the presence of pro and anti-inflammatory factors, and the PD-L1/PD-1 signaling was blocked by anti PD-L1 mAbs. Allo-stimulatory capacity of DCs was impaired, and inversely correlated with PD-L1/CD86 ratio. However, blocking PD-L1 on DCs increased of Th1 and Th17 proliferation, concomitant with a Tregs reduction, independently of the DCs phenotype and functional characteristics. We demonstrated that the PD-L1/CD86 ratio play a key role in the functional capability of DCs. Therefore, blocking this molecule on DCs becomes an attractive strategy to improve the efficacy of DCs-based vaccines in melanoma patients.