MINIMa: Modulation of Immunogenicity of regulated Necrosis by 3d bio-prIntable MAterials (MINIMa)

Physiological cell death, called apoptosis, typically does not induce an immune response –ut it

rather suppresses it- and is therefore non-immunogenic or even immuno-suppressive. Recently, it

has been discovered that besides apoptosis there are other regulated cell death modalities, which

are grouped under the umbrella term regulated necrosis. The type of cell death is a decisive

element in determining the quality and quantity of the immune response. We have reported that

necroptosis, a form of regulated necrosis, is immunogenic (stimulatory) and induce anti-tumour

immunity and protect the host against the tumour. 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. Therefore the major aim of this proposal is to fully understand the immuno-modulatory

role of different cell death modalities in a 3D context. Moreover it is 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 response.