Mathematical model of tumor–immune surveillance. (7th September 2016)

• Record Type: Journal Article
• Authors: Mahasa, Khaphetsi Joseph; Ouifki, Rachid; Eladdadi, Amina; Pillis, Lisette de
• Is Part Of: Journal of theoretical biology. Volume 404(2016)
• Page Start: 312
• Page End: 330
• Publication Date: 2016-09-07
• Subjects: Mathematical model -- Immune surveillance -- Tumor escape -- Immunotherapy; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2016.06.012
• Languages: English
• ISSNs: 0022-5193

Abstract

Abstract: We present a novel mathematical model involving various immune cell populations and tumor cell populations. The model describes how tumor cells evolve and survive the brief encounter with the immune system mediated by natural killer (NK) cells and the activated CD8 + cytotoxic T lymphocytes (CTLs). The model is composed of ordinary differential equations describing the interactions between these important immune lymphocytes and various tumor cell populations. Based on up-to-date knowledge of immune evasion and rational considerations, the model is designed to illustrate how tumors evade both arms of host immunity ( i.e. innate and adaptive immunity). The model predicts that (a) an influx of an external source of NK cells might play a crucial role in enhancing NK-cell immune surveillance; (b) the host immune system alone is not fully effective against progression of tumor cells; (c) the development of immunoresistance by tumor cells is inevitable in tumor immune surveillance. Our model also supports the importance of infiltrating NK cells in tumor immune surveillance, which can be enhanced by NK cell-based immunotherapeutic approaches. Abstract : Highlights: Tumor escape is a major impediment for the success of most immunotherapeutic approaches. Tumor cells employ various mechanisms to evade immune surveillance. We model how tumor cells evade both arms of host immunity ( i.e. innate and adaptive immunity). The model predicts that a low number of key immune cells might lead to tumor escape. The robustness of the model predictions to parameter uncertainties is ascertained using a global sensitivity analysis.