Abstract. Eliminating immunosuppressive cells, such as regulatory T cells (Tregs), is a promising approach to boost immunotherapy success. However, this approach may suffer from systemic auto-immune adverse events, highlighting the need to specifically target tumor-infiltrating (ti)Tregs. We identified IL1R2 as a surface marker that was most highly expressed by activated and strongly T-cell suppressive tiTregs in the tumor microenvironment but not by peripheral Tregs. IL1R2 activity itself was dispensable for tiTreg abundance and activation and did not influence tumor growth. Hence, we used IL1R2 as anchor molecule for the specific elimination of tiTregs. Indeed, anti-IL1R2 Nb-Fc constructs with an optimized ADCC functionality resulted in the specific depletion of IL1R2+ tiTregs, elicited antitumor immunity and reduced tumor growth, in synergy with anti-PD-1 therapy.
Authors. Sana M. Arnouk; Daliya Kancheva; Helena Van Damme; Guillaume E. Courtoy; Romina Mora Barthelmess; Jolien Van Craenenbroeck; Els Lebegge; Yvon Elkrim; Naela Assaf; Yves Heremans; Aleksandar Murgaski; Timo W M. De Groof; Emile Clappaert; Ayla Debraekeleer; Jan Brughmans; Gillian Blancke; Máté Kiss; Ramses Forsyth; Wim Waelput; Louis Boon; Nick Devoogdt; Catelijne Stortelers; Nadja van Boxel; Bruno Dombrecht; Lars Vereecke; Cécile Vincke; Geert Raes; Damya Laoui; Jo A. Van Ginderachter.
Belgian Immunological Society 