In Vitro Veritas: From 2D Cultures to Organ-on-a-Chip Models to Study Immunogenic Cell Death in the Tumor Microenvironment

Author:

Krysko Dmitri V.ORCID,Demuynck RobinORCID,Efimova Iuliia,Naessens FayeORCID,Krysko Olga,Catanzaro ElenaORCID

Abstract

Immunogenic cell death (ICD) is a functionally unique form of cell death that promotes a T-cell-dependent anti-tumor immune response specific to antigens originating from dying cancer cells. Many anticancer agents and strategies induce ICD, but despite their robust effects in vitro and in vivo on mice, translation into the clinic remains challenging. A major hindrance in antitumor research is the poor predictive ability of classic 2D in vitro models, which do not consider tumor biological complexity, such as the contribution of the tumor microenvironment (TME), which plays a crucial role in immunosuppression and cancer evasion. In this review, we describe different tumor models, from 2D cultures to organ-on-a-chip technology, as well as spheroids and perfusion bioreactors, all of which mimic the different degrees of the TME complexity. Next, we discuss how 3D cell cultures can be applied to study ICD and how to increase the translational potential of the ICD inducers. Finally, novel research directions are provided regarding ICD in the 3D cellular context which may lead to novel immunotherapies for cancer.

Funder

FWO-Flanders

Ghent University BOF

FWO and F.R.S.-FNRS under the Excellence of Science

Robin Demuynck

Iuliia Efimova

Faye Naessens

Russian Science Foundation

Publisher

MDPI AG

Subject

General Medicine

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