The role of CD200–CD200R in tumor immune evasion

Interleukin-12 is a pro-inflammatory cytokine which promotes Th1 and cytotoxic T lymphocyte activities, such as Interferon- secretion. For this reason Interleukin-12 could be a powerful therapeutic agent for cancer treatment. However, Interleukin-12 is also excessively toxic. Interleukin-27 is an immunoregulatory cytokine from the Interleukin-12 family, but it is not as toxic as Interleukin-12. In recent years, Interleukin-27 has been considered as a potential anti-tumor agent. Recent experiments in vitro and in vivo have shown that cancer cells transfected with IL-27 activate CD8+ T cells to promote the secretion of anti-tumor cytokines Interleukin-10, although, at the same time, IL-27 inhibits the secretion of Interferon- by CD8+ T cells. In the present paper we develop a mathematical model based on these experimental results. The model involves a dynamic network which includes tumor cells, CD8+ T cells and cytokines Interleukin-27, Interleukin-10 and Interferon-. Simulations of the model show how Interleukin-27 promotes CD8+ T cells to secrete Interleukin-10 to inhibit tumor growth. On the other hand Interleukin-27 inhibits the secretion of Interferon- by CD8+ T cells which somewhat diminishes the inhibition of tumor growth. Our numerical results are in qualitative agreement with experimental data. We use the model to design protocols of IL-27 injections for the treatment of cancer and find that, for some special types of cancer, with a fixed total amount of drug, within a certain range, continuous injection has better efficacy than intermittent injections in reducing the tumor load while the treatment is ongoing, although the decrease in tumor load is only temporary.

show abstract

“…Since IL-27 belongs to the IL-12 family, we take its diffusion coefficient and the degradation rate to be the same as for IL-12 [48]: …”

Section: Methodsmentioning

confidence: 99%

“…From [48], we have . To estimate , we consider the case of J558-Ctrl tumor cells, for which the term with is removed from (19): …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Mathematical Modeling of Interleukin-27 Induction of Anti-Tumor T Cells Response

2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…CD200 has been well characterized as an immunosuppressive protein that inhibits immune responses through its receptor [9][10][11]. In healthy individuals, CD200 is distributed on a wide variety of tissues, including B cells, activated T cells, certain vascular endothelia, kidney, placenta cells and neurons [12].…”

mentioning

confidence: 99%

Tumor-Derived Vaccines Containing CD200 Inhibit Immune Activation: Implications for Immunotherapy

et al. 2016

View full text Add to dashboard Cite

There are over 400 ongoing clinical trials using tumor-derived vaccines. This approach is especially attractive for many types of brain tumors, including glioblastoma, yet so far the clinical response is highly variable. One contributor to poor response is CD200, which acts as a checkpoint blockade, inducing immune tolerance. We demonstrate that, in response to vaccination, glioma-derived CD200 suppresses the anti-tumor immune response. In contrast, a CD200 peptide inhibitor that activates antigen-presenting cells overcomes immune tolerance. The addition of the CD200 inhibitor significantly increased leukocyte infiltration into the vaccine site, cytokine and chemokine production, and cytolytic activity. Our data therefore suggest that CD200 suppresses the immune system's response to vaccines, and that blocking CD200 could improve the efficacy of cancer immunotherapy.

show abstract

“…It is a member of the highly conserved immunoglobulin family, and it is expressed in myeloid cells, such as macrophages, dendritic and mast cells, and eosinophils. Interactions between CD200 and its receptor CD200R act as an immune tolerance signal, which reduces myeloid cell activity and change their migration ability (9)(10)(11)(12). In recent years, high CD200 expression was found in colon cancer, myeloma, breast and brain cancer, melanoma and normal mesenchymal stem cells.…”

Section: Introductionmentioning

confidence: 99%

Identification of CD200+ colorectal cancer stem cells and their gene expression profile

Zhang

Huang

et al. 2016

Oncology Reports

View full text Add to dashboard Cite

CD200 is a cell surface glycoprotein that has been implicated in a variety of human cancer cells. It has been proposed as a cancer stem cell (CSC) marker in colon cancer and is closely related to tumor immunosuppression. However, there is little functional data supporting its role as a true CSC marker, and the mechanism by which CD200 contributes to colorectal cancer has not been elucidated. In the present study, CD200+ and CD200- COLO 205 colorectal cancer cells were sorted out by flow cytometry, and colonosphere formation and Transwell migration assays were performed. Affymetrix Human U133 Plus2.0 arrays were used to screen the gene expression profiles of CD200+ and CD200- colorectal cancer cells. The results suggest that there are differentially expressed genes between the two subpopulations, including several important genes that function in cell proliferation, metastasis, apoptosis and the immune response. Pathway analysis revealed that the Wnt, MAPK and calcium signaling pathways were differentially expressed between CD200+ and CD200- cells. Moreover, several key genes upregulated in CD200+ cells were also highly overexpressed in CD44+CD133+ colorectal stem cells compared to the CD44-CD133- fraction of the same cell line. In the present study, we showed for the first time a correlation between CD200 expression and the Wnt signaling pathway in colon cancer cells.

show abstract

The role of CD200–CD200R in tumor immune evasion

Cited by 29 publications

References 64 publications

Mathematical Modeling of Interleukin-27 Induction of Anti-Tumor T Cells Response

Mathematical Modeling of Interleukin-27 Induction of Anti-Tumor T Cells Response

Tumor-Derived Vaccines Containing CD200 Inhibit Immune Activation: Implications for Immunotherapy

Identification of CD200+ colorectal cancer stem cells and their gene expression profile

Contact Info

Product

Resources

About