CD200fc enhances anti-tumoral immune response and inhibits visceral metastasis of breast carcinoma

Abstract

CD200 is a widely expressed cell surface glycoprotein that inhibits excessive inflammation in autoimmunity, transplantation, and viral infections. We previously observed that visceral metastasis of highly aggressive and inflammatory 4THM breast carcinoma cells was markedly decreased in CD200 transgenic mice. The goal of this study was to determine whether exogenous exposure to CD200fc mimics the effects of endogenously over expressed CD200. Female BALB/c mice were injected with CD200fc two times a week for five times. Injection was started two days after orthotopic injection of 4THM cells. Tumor infiltrating Gr1+Cd11b+ cells were decreased while CD8+ cells were increased in CD200fc-treated animals. CD200fc injection significantly decreased lung and liver metastasis and the growth of primary tumors. CD200fc injection enhanced the tumor-induced IFN-g response while suppressing the IL-10 response. We observed excessive basal IL-6 secretion in MLC which was significantly decreased in CD200fc treated mice 12 days after injection of 4TM cells. These results are in accord with previous data from CD200 transgenic mice, and demonstrate for the first time that CD200 analogues might have therapeutic potential in the treatment of aggressive breast carcinoma which induces excessive systemic inflammation.

Inhibitory CD200-receptor signaling is rewired by type I interferon

“…However, the CD200R-CD200 axis has also been reported as a co-stimulatory axis (Borriello et al, 1997;Wang et al, 2019). Furthermore, CD200R is required to 'license' TLR2mediated immune activation by Herpes Simplex Virus 1 in macrophages (Soberman et al, 2012), and the CD200R/CD200 axis in some cases was suggested to regulate protective antitumor responses (Erin et al, 2015;Erin et al, 2018;Liu et al, 2016). Taken together, although CD200R is generally considered to be an inhibitory receptor, there are data that suggest a more versatile and/or complex functionality of CD200R.…”

Prognostic Value of CD200R1 mRNA Expression in Head and Neck Squamous Cell Carcinoma

“…Collectively the associations between CD200R1 and these diverse immune-related proteins suggest that CD200R1 is involved in a variety of immune mechanisms and may explain why HNSCC with high CD200R1 expression is related to an 'immune-rich' microenvironment with high immune cell estimates. Thus, our findings suggest that modulation of the CD200R1 pathway could be used as an immunotherapeutic strategy in patients with HNSCC [22,35,36].…”

“…Several potential mechanisms have been associated with CD200R1 and immune responses [17,20,22]. For instance, 4THM breast cancer cell growth and invasion were increased in CR200R1KO mice and decreased in mice over-expressing CD200, with a lack of CD200R1 expression related to decreased CD8 + and CD3 + CD25 + T cells [23].…”

“…In contrast, CD200 overexpression in CD200 transgenic mice was found to increase tumor-induced IFN-γ and decrease inflammatory cytokine, TNF-α, and IL-6 expression. Moreover, CD200fc, which mimics the effect of CD200, significantly decreased tumor growth and metastasis in a mouse model of breast cancer, increased IFN-γ and decreased IL-6 expression, and time-dependently altered IL-10 and IL-17 levels [22]. In this study, we analyzed genes that are biologically related to CD200R1 using the STRING database and by conducting a literature review.…”

CD200:CD200R Interactions and Their Importance in Immunoregulation

“…In preliminary studies, growth of tumor in this model was attenuated using therapy with anti-CD200mAb and was associated with augmented host anti-tumor immunity [ 94 ]. Interestingly, use of CD200fc, which is an CD200R1 agonist, significantly decreased the growth of metastatic breast cancer 4THM cells due to the inhibition of cancer-related inflammation and increase both the tumor-infiltrating CD8+ T cell number and tumor-induced IFN-γ secretion [ 95 ].…”