The roles of CD200-CD200R and Interleukin-12 cytokine family in cancer immunoediting
Mathematical Biosciences Institute, The Ohio State University
(February 27, 2014 10:20 AM - 11:15 AM)
Cancer immunoediting is to study the balance between tumor cells and immune system. There are many important factors and mechanisms that play significant roles in cancer immunoediting, such as CD200-CD200R and Interleukin-12 (IL-12) cytokine family.
CD200 is a cell membrane protein that interacts with CD200 receptor (CD200R) of myeloid lineage cells. During tumor initiation and progression, CD200-positive tumor cells can interact with M1 and M2 macrophages through CD200-CD200R-compex to silence macrophages. However, this mechanism has been shown to have apparently two contradictory experimental results in tumor growth: inhibition and promotion. In this talk, I will introduce a system of partial differential equations that we constructed to explain why these two opposite experimental results can both take place depending on the "affinity" of M1 and M2 macrophages to form the complex CD200-CD200R with tumor.
The Interleukin-12 (IL-12) cytokine family, which is composed of heterodimeric cytokines, includes IL-12, IL-23, IL-27, and IL-35. IL-12 and IL-23 are mainly pro-inflammatory cytokines with key roles in the development of the TH1 and TH17 subsets of helper T cells, respectively. IL-27 has been regarded as an immunoregulatory cytokine, due to both of pro-inflammatory and anti-inflammatory functions in anti-tumor activity. Notably, recent experiments in transgenic mice indicate that IL-27 significantly enhances the survival of activated tumor antigen specific CD8+ T cells and hence promotes tumor rejection. IL-35, the most recently identified member of IL-12 cytokine family, is a potent inhibitory cytokine pro-duced by regulatory T cells. Recent transgenic mouse experiments demonstrate that IL-35 enhances the tumor growth and angiogenesis. Hence, I will also introduce another two mathematical models for IL-27 and IL-35 that we constructed to study the functions of IL-27 and IL-35. These models qualitatively fit with the above experimental results and provide some hypotheses to develop therapeutic protocols in cancer treatment.