Immunogenicity of cancer cells undergoing regulated necrosis in three-dimensional microenvironment

Inducing immunogenic (immunostimulatory) apoptotic cell death in cancerous cells is very beneficial

because it induces a host anti-tumour immune response. However, often tumors develop apoptosis

resistance and induction of immunogenic apoptosis is not any more an option. In order to overcome

apoptosis resistance, it is of great importance to find other ways to kill tumor cells by triggering cell

death modalities different from apoptosis. Recently, it has been discovered that besides apoptosis

there are other cell death modalities, which are grouped under the umbrella term regulated

necrosis. Until now most of the work on immunomodulatory characteristics of dead cancerous cells

was done by using two-dimensional systems (2D), which does not fully recapitulate in vivo

interaction of dying cells with the immune system. However, in recent years, it has become clear

that bioprinting of cancerous cells with biomaterials can create a three-dimensional (3D)

microenvironment overcoming the limits of 2D cultures. The major aim of this proposal is to fully

understand the immuno-modulatory role of tumour cells undergoing different cell death modalities

in a 3D context. It is conceivable that immunostimulatory biomaterials may lead to synergistic

immunogenic effects of dying cancerous cells. Next, we want to investigate whether combining

immunostimulatory biomaterials and immunogenic cell death modalities will lead to an enhanced

anti-tumour immune response.