TLR3 ligand Poly A:U modifies the composition of the tumour-infiltrating myeloid compartment towards an anti-tumour phenotype

ROSELLI E.; ARAYA P.; NOCERA D; NÚÑEZ N.G.; TRUCCO L.D.; MACCIONI M.

Buenos Aires

Congreso; First International Joint Meeting between the French Society for Immunology, the Latin American Society for Immunodeficiencies, and the Argentine Society for Immunology; 2015

Abstract: Poly A:U (pAU) is a dsRNA which signals throughTLR3 to modulate an immune response by inducing the release oftype I IFNs on a broad range of cells including cancer cells andtumour- associated myeloid populations. Relaying on this, pAUcan be exploited as an immune-adjuvant on cancer therapy toimprove an antitumor immune response. In this work, weevaluated the effect of pAU treatment on a murine B16 melanomacancer model focusing on the myeloid compartment, morespecifically on tumour-associated macrophages (TAMs) definedas CD45+; CD11b+; CD68+; LyC6-. We demonstrated that athree doses regime of intratumoral treatment with pAU(50µg/tumour) significantly decreases tumour size from 2.2g to0.78g (p < 0.05), and increases the density of infiltratingleukocytes from 0,6.107/g to 1,1.107/g compared to PBS-treatedmice. Within tumour-infiltrating leukocytes, plasticity and cellpolarization of TAMs are key aspects to define a final antitumoral(M1) or protumoral (M2-like) outcome. Here we described a decrease in the frequency of M2-like (CD45+; CD11b+; CD68+;LyC6-; CD206+) TAM polarization from 6.8% to 3,9% (p < 0.05)of all CD45+ cells as well as in number from 7,7.105 to 3,3.105 (p< 0.05) when tumours were treated with pAU. This M2-likepopulation also accounts for most of the intratumoral IL10production as seen by flow cytometry; by reducing this protumoralM2-like population pAU exerts an antitumor effect.