The role of Natural Killer cells in the development of a primary tumour mass and metastasis formation

11 Jul 2018, 16:00
New Law School/--024 (University of Sydney)

New Law School/--024

University of Sydney

Oral Presentation Minisymposium: Modelling immune interactions with disease Modelling immune interactions with disease


Ms Victoria Gershuny (University of Arizona)


In recent years, advances in cancer research have shown that the body’s immune response to tumour cells plays a significant role in fighting cancer growth. Although the immune system is intrinsically capable of destroying tumour cells, tumours and their microenvironment have an ability to suppress the immune response. Whereas the roles of some immune cells have been greatly studied, the role of Natural Killer (NK) cells is less clear. Despite the fact that studies have shown that NK cells are not very effective at penetrating the tumour environment and play a minimal role in the direct killing of tumour cells in a tumour mass, studies with NK cell immunotherapies in humans have shown great success. The leading cause of death for cancer is not primary tumour growth, but instead metastasis formation. In mice, depleting NK cells has shown to prevent metastasis formation. In order to understand the complex interplay between the primary tumour, the metastases, and the immune system, it is necessary to develop a model of tumour growth that includes these immune subpopulations and their interactions with the tumour and with each other. Here, such a model is presented, consisting of 17 coupled ordinary differential equations and one stochastic ODE that capture the complex interplay between CD4+ and CD8+ T cells, regulatory T cells, NK cells, dendritic cells, MDSCs, and both immunostimulatory (IL-2, IFN-gamma) and immunosuppressive (IL-10, TGF-beta) cytokines or factors, the primary tumour, circulating tumour cells, and tumour metastases. All parameters are estimated from experimental data. The model shows that one of the main immune components contributing to the prevention of metastasis formation is killing of circulating tumour cells by NK cells. For tumours with high antigen expression on their surface, T cells play the primary role in preventing metastasis formation, however circulating tumour cells with low antigen expression are eradicated mostly by NK cells. With this model, it is possible to replicate experimental data of metastasis formation under NK cell depletion. Implications for considering immunologic effects of standard chemotherapy combinations, in particular FOLFOX for colorectal cancer, are discussed.

Primary authors

Ms Victoria Gershuny (University of Arizona) Timothy Secomb (University of Arizona) Mrs Ardith El-Kareh (University of Arizona)

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