A TLR-4 agonist induces the recruitment of tumour infiltrating lymphocytes in melanoma-bearing mice and improves immune checkpoint blockade treatment

GIL CAMILA; GOLDIN CARLA; BERGUER PAULA; FARIAS ANA; GOLDBAUM FERNANDO

Mar del Plata

Congreso; Reunión anual SAI-SAIC-SAFIS; 2018

Brucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells (DCs) via TLR4, inducing the upregulation of costimulatory molecules and the secretion of proinflammatory cytokines and chemokines. Due to BLS structure, proteins can be fused to its 10 N-termini, constituting a proven platform for the development of vaccines. The chimera BLS-OVA (containing ovalbumin peptide 257-264) induces the cross presentation of the peptide and a specific CTL response through TLR4 signalling. We have shown that BLS and BLS-OVA have a therapeutic effect in B16F1-OVA-expressing melanoma-bearing mice only when administrated at early stages of tumour growth. In order to study the triggered mechanisms, we analysed the tumour infiltrating lymphocytes. B16F1-OVA-expressing cells were s.c. inoculated in C57/Bl6 mice and after 2 or 10 days 200µg of BLS was administrated. At day 14 tumours were analysed through flow cytometry. Administration of BLS at day 2 but not at day 10 induces the recruitment of immune cells (10,39%±6,080 and 2,75%±0,6218; p