Immunotherapy based on the TLR3 ligand Poly A:U modifies the tumor-associated myeloid compartment upregulating PDL1 specifically on MHCII monocytes on a type I IFN-dependent manner

ROSELLI, E; ARAYA, P; NUÑEZ, NG; STEMPIN, CC; PIAGGIO, E; MACCIONI, M

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. LXV Reunión Sociedad Argentina de Inmunología.; 2017

Poly A:U (pAU) is a synthetic 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. Relying on this, pAU canbe exploited as an immune-adjuvant on cancer therapy to improvean antitumor immune response. In this work, we evaluated the effectof pAU treatment on a murine B16 melanoma cancer modelfocusing on the myeloid compartment, including tumour-associatedmacrophages (TAMs - CD45+; CD11b+; F4/80+; LyC6-; CD24-), tumour-infiltrating DCs (CD45+; CD11b+; CD24+; CD11c+; MHCII+), togetherwith tumour-associated monocytes (CD45+; CD11b+; Ly6C+;CCR2+) which can be divided into MHCII+ and MHCII- monocytes.We demonstrated that a three-dose regime of intratumoral treatmentwith pAU (100μg/tumour) significantly decreases tumour size from0.33g to 0.15g (p