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Hybrid Tumour Models to Understand Cancer’s Tricks against the Immune System

Research

The immune system recognises and eliminates abnormal cells, such as virus-infected cells or cancer cells. However, cancer cells can develop strategies to evade this control: they block defence mechanisms or send inhibitory signals. In this way, tumours can grow unchecked. In a collaborative study, research teams from Germany, the United Kingdom, and Hungary have developed hybrid tumour models from the self-assembly of cancer cells and artificial cells. Their study, published in Nature Communications, offers a new approach for studying and characterising the mechanisms that enable cancer cells to evade the immune system, as well as new perspectives for designing hybrid materials.

Potato-shaped conglomerate composed, on the left side, of opaque circular shapes in various colours (brown, cyan, magenta, and green) and, on the right side, of slightly transparent and fluorescent circular shapes (cyan and magenta).
Schematic illustration and actual image of a 3D hybrid culture of cancer cells and synthetic cells (in magenta).

Why hybrid systems matter for cancer research

The use of living 3D cancer cultures, known as tumoroids, has advanced cancer research, revealing new mechanisms behind this leading cause of death worldwide. However, in vivo, non-cancerous cells are present in the tumour microenvironment and interact with cancer cells. These interactions, including immune responses, are difficult to reproduce in tumoroids.

In this study, researchers developed an approach to study how cancer cells interact with immune cells, and more specifically, how they evade our immune system, without the need for real immune cells. They reconstructed a tumour immune microenvironment from scratch through the self-assembly of cancer cells with what they refer to as ‘synthetic cells’, biomimetic materials that reproduce some of the characteristics of natural cells.

Choosing the right synthetic cell chassis model

There is a wide range of synthetic cellular chassis, each offering different advantages for reproducing certain aspects of living cells. These include giant unilamellar vesicles, coacervate microdroplets, colloidosomes, polymerosomes, and droplet-supported lipid bilayers (DSLBs).

Scientists assessed the integration capacity of these different chassis and determined the integration mechanism for forming hybrid tumour models. They showed that DSLBs were strong candidates for self-assembling hybrids. In addition, they demonstrated that integration was mediated by inter- and extracellular adhesion forces and by the surface tension of the chassis, a crucial insight for the future design of interfaces between synthetic and natural cells.

Mimicking immune cells to study interactions between cancer and immune cells

To create immune cell mimics and form the hybrid tumoroid, the team functionalised the DSLBs so that they could interact with cancer cells and produce signals similar to those normally produced by immune cells. They then studied how cancer cells evade attacks from the immune system in the case of pancreatic cancer.

“With our model, we can track how tumours trick and block the immune system,” explained Oskar Staufer from the INM – Leibniz Institute for New Materials in Saarbrücken. “In the case of pancreatic cancer, a particularly aggressive type, we were able to discover a new mechanism by which the cancer selectively disables immune cells.”

Future directions

This insight opens the door to intentionally designing artificial tumour environments in the future. Looking ahead, Nils Piernitzki, first author of the study, said: “So far, we have focused on a simple experimental setup to evaluate the potential of the model. Next, we aim to replicate the tumour environment in the human body as realistically as possible.”

In the long term, this method could not only advance cancer research but also create new approaches for combining “living” and “non-living” components in innovative medical materials.

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