What are Natural Killer cells doing in cancer?
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Speaker
Abstract
In recent years, advances in cancer research have shown that the body’s immune response to tumor cells plays a significant role in fighting cancer growth. 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 tumor environment and play a minimal role in the direct killing of tumor cells in a tumor mass, studies with NK cell immunotherapies have shown great potential. This is suspected to occur through metastasis formation. In order to quantify the actual role of NK cells, a model was developed, consisting of 17 coupled ordinary differential equations and one stochastic ODE that capture the complex interplay between the primary tumor, the metastases, and the immune system. All parameters were 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 tumor cells by NK cells. For tumors with high antigen expression on their surface, T cells play the primary role in preventing metastasis formation, however circulating tumor 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 and treatment with a standard chemotherapy, FOLFOX, for colorectal cancer.