Antitumor activity of TLR7 is potentiated by a CD200R antibody leading to a change in mouse tumor microenvironment
Zofia Pilch12, Katarzyna Tonecka12, Louis Boon3, Jakub Golab1, Linde Meyaard4, Tomasz P. Rygiel1
1 Department of Immunology, Medical University of Warsaw, Warsaw, Poland
2 School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
3 Bioceros BV, Utrecht, The Netherlands
4 Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
Stimulation of Toll-like receptor 7 (TLR7) signaling activates myeloid cells and boosts the immune response. Previously, we showed that stimulation of the inhibitory CD200 receptor (CD200R) suppresses TLR7 signaling and that the absence of CD200R-signaling leads to a decreased number of induced papillomas in mice. Here we investigate the effects of anti-CD200R on the antitumor activity of a TLR7 agonist (R848) in syngeneic mouse tumor models. Intratumor administration of R848 inhibited growth of the CT26 colon carcinoma in mice, simultaneously decreasing CD200R expression on tumor-infiltrating immune cells. The antitumor effects of R848 were potentiated by anti-CD200R. Successfully treated mice proved to be resistant to rechallenge with the same tumor. R848 administration was more effective in inhibiting B16F10 melanoma growth in C57BL/6 Cd200-/- mice, lacking CD200R signaling, compared to wild-type mice. Administration of R848 combined with anti-CD200R changed the composition of intratumor myeloid cells by decreasing the fraction of macrophages in favor of monocytes. Combined treatment decreased intratumoral expression of the macrophage markers F4/80 and CD206, while it increased production of IL-6 and arginase-1, suggesting a shift to pro-inflammatory myeloid cells. Based on these findings, we conclude that application of anti-CD200R combined with a TLR7 agonist, improves the antitumor effects of TLR7 signaling and leads to a change in the local tumor microenvironment, supporting immune activating stimulation. We propose that use of anti-CD200R in combination with TLR7 stimulation may be of value as an anticancer treatment.