A few weeks ago, our consortium got together to reflect on the pace of our research and provide an update on the work of our doctoral candidates since they started. Below, we have compiled summaries of these updates to share with you:

Epistemic inclusion in cancer research – Simon Gramvik

My project explores how cancer research can become more inclusive by involving patient partners, their perspectives, experiences, and values, from the very beginning of the research process.

I am currently developing two studies. The first examines how the “patient voice” is shaped through participation in peer communities and patient organizations. Based on interviews with prostate and breast cancer patients, it explores how peer exchange and organizational norms influence how individuals understand and communicate their illness experiences. The second investigates the role of brokers who connect researchers with patient partners, reflecting on how their recruitment choices and routines shape which kinds of knowledge are included.

The plan is to start interviews in January 2026.

Spatial multiplexed immunofluorescence profiling of patient tumor tissue samples – Sidney van der Zande

In my project, I explore how the location of cells in the tumor and the cells that are close to them shape patient prognosis and response in different types of metastatic cancer. At the moment, I am working on finalizing an analysis pipeline to be able to identify different types of cells from microscope images. I am testing multiple methods to extract different features from these images and comparing these methods to see how we can use them optimally. In the next few months, I will be working on analyzing the results from these analyses and trying to correlate our findings to patient outcomes. From this, we hope to identify potential prognostic factors that we can translate to clinical tests.

How the Bone Environment Affects Prostate Cancer Treatment – Caroline de Aquino Guerreiro

My project focuses on understanding the sensitivity of prostate cancer (PCa) cells to Standard-of-Care (SoC) therapies within an age-relevant, bone-specific microenvironment. I am establishing protocols to isolate human PBMCs, differentiate and polarize macrophages, and develop co-culture systems with PCa cells. Concurrently, I am optimizing 3D spheroid models (PC-3) to better mimic the metastatic niche. Using these models, I have tested docetaxel and the immune-derived metabolite itaconate (4-OI), determining IC₅₀ concentrations and analyzing effects on viability, migration, and cell metabolism. Notably, 4-OI modulates tumor cell behavior but does not protect cells from chemotherapy-induced cytotoxicity.

Next steps include optimizing spheroid formation, investigating 4-OI effects on gene expression, metabolism, and proliferation, expanding SoC treatments to include radiotherapy, and performing macrophage–tumor co-culture experiments to assess cellular interactions and treatment responses.

Identification, Characterization and Manipulation of Glycosaminoglycans in Ageing and Cancer – Avika Srivastava

My project focuses on characterizing and investigating glycosaminoglycans (GAGs) in the contexts of ageing and cancer. These sugars play key structural and signaling roles due to their abundance in the extracellular matrix (ECM). To examine GAG composition and spatial distribution, I use Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), a high-resolution technique capable of providing chemical and spatial mapping, aligned with multiplex technologies. Using this approach, I have been analyzing region specific GAG profiles in breast and ovarian cancer cores.

The next phase of my work involves comparing GAG concentrations within the ECM of breast-cancer-derived fibroblasts and tumour-associated fibroblasts using an in vitro cell-derived matrix system. Additionally, I will incorporate macrophages into the model to evaluate tumour–macrophage interactions and their effects on GAG expression and organization, with the aim of better understanding microenvironmental regulation of GAGs within tumour-associated ECM.

Building a model of prostate cancer metastasis into the liver organ – Lennart Linke

I am working with a microfluidic device, a so called “Organ-on-a-chip”, to study the process of prostate cancer cells invading, or metastatzing into the liver.

Currently I am working on the two core elements of the model: The liver spheroid, a kind of cell aggregate as well as optimizing the model settings to circulate cancer cells trough small tubes, modeling the blood circulation in the human body.

Moving the spheroids from a static petri dish into the chip where they constantly exposed to a liquid flow is major change for this delicate structure. That’s why I am currently determining for how long the cells are alive and expressing liver functions, to make sure my model reflects the biological reality in a patient.

For the prostate cancer cells, I need to ensure that they are also alive under flow conditions, so they can invade the liver spheroid. In a technical setting, I am optimizing my flow and cell media conditions that my system can circulate a sufficient number of cells so I can observe the metastatic processes.

Once all parameters, I will combine my results to deliver a liver model in the chip with circulating cancer cells, which can invade the liver spheroid.

Simulating bone metastasis with a Bone-on-a-Chip – Apostolos Papadopoulos

My work revolves around creating and optimising a “Bone-on-a-Chip” as a system that can mimic early bone metastasis. I am currently focusing on optimising my 3D cultures of Mesenchymal Stromal Cells (MSCs) by adjusting the collagen scaffold to figure out which conditions best allow the cells to grow. Very recently, I started staining my hydrogels for cell viability, and I plan to try different stains over the next few weeks. I have also received the microfluidics system, the MIVO, which will be the basis of my chip. I have already set it up, and I will start testing with cancer cells by the end of November.

The next step will be to combine the two and have an operational MIVO chip with collagen in the insert. The hydrogel will only contain MSCs at the beginning, with macrophages, osteoclasts, and potentially other cell types being added in the future. Prostate cancer cells will flow with the medium and will hopefully invade the scaffold.

Bespoke Hydrogels for Modelling Cancer Metastasis to the Liver -Elena Montero-Bragado

To better understand cell-matrix interactions in the liver and develop a model that is as human-relevant as possible, my recent work has focused on designing an appropriate 3D environment for liver cells. I have been optimizing the mechanical properties of animal-free hydrogels, particularly their storage and loss moduli, and enhancing their biological functionality by incorporating relevant extracellular matrix peptides. I then evaluated how these modifications influenced the viability of embedded HepG2 cells.

The next steps will involve assessing not only cell survival but also cellular function, such as albumin secretion. In parallel, I plan to replace the immortalized HepG2 line with a healthier and more physiologically relevant model, likely by developing a protocol to generate liver organoids from iPSC-derived cells. Achieving these goals will enable the incorporation of immune cells and additional liver components, enhancing the complexity and relevance of the model.

Impact of the Liver Microenvironment on Therapy Response in Metastasized Prostate and Breast Cancer – Loona Meyer

In my project, I am studying how prostate and breast cancer cells respond to standard treatments within the context of liver metastases, focusing on the influence of the liver-specific and age-related microenvironment on therapeutic outcomes.

Currently, I am establishing a stable, reproducible experimental platform for semi-high-throughput drug testing. This involves optimizing liver model generation and hydrogel embedding, as well as establishing a pre-screening quality control for drug assays. Additionally, I am developing a co-culture system combining 3D liver models with prostate cancer cells to mimic a metastasized liver environment. Another task is comparing differentiation and polarization protocols for PBMC-derived macrophages. For validation, I am utilizing flow cytometry and optimizing a panel of differentiation/polarization markers.

My next steps will focus on bringing these single parameters together, optimizing the experimental setup and testing standard of care treatments.

Generation, differentiation, and functional features of organ-specific macrophages and the impact of macrophage ontogeny on interaction with metastasising tumour cells – Viktor Georgiev

In my project, I am investigating how tissue-resident macrophages interact with invading cancer cells in the early stages of metastasis. More specifically, I am focusing on Kupffer cells, microglia, and osteoclasts, which are the resident macrophages of the liver, the brain, and the bones, respectively. As a source of macrophages, I intend to use induced pluripotent stem cells (iPSCs). Thus, I am currently working on setting up and optimising protocols for differentiating tissue-resident macrophages from iPSCs. My preliminary data suggests that we have already produced early macrophage progenitors from iPSCs. In the near future, I will further optimise and upscale the macrophage generation protocol and set up assays for testing the functionality of the produced macrophages. In the long run, we plan to include our iPSC-derived macrophages in Organ-on-Chip systems to model the innate immune response to infiltrating tumour cells.

Macrophages Response to the Neuroblastoma Cell Invasion in an Organ-on-a-Chip Model – Chunyu Yan

This project focuses on establishing a biomimetic organ-on-a-chip platform to investigate neuroblastoma metastasis into the brain. Key progress includes the successful fabrication of the chip device and the synthesis of a tunable 3D NorHA (norbornene-functionalized hyaluronic acid) hydrogel designed to replicate the brain’s extracellular matrix. We have performed initial mechanical stiffness characterization of the hydrogels and successfully seeded neuroblastoma cells within this 3D environment, confirming initial cell viability and establishing our core methodology.

Our immediate future work will concentrate on refining the NorHA hydrogel system. This involves optimizing its biochemical composition by incorporating key bioactive cues and systematically characterizing its mechanical properties to better mimic the soft brain tissue. This optimized platform will be foundational for subsequent investigations into the mechanisms of neuroblastoma cell invasion and colonization within a physiologically relevant model.

Identification of microglia function and matrix composition changes induced by the first interaction with invading prostate cancer (PCa) cells in the mini-brain OoC model – Marine Cuiller

To study early metastatic processes and how cancer cells reshape the brain microenvironment into an immunosuppressive niche, I am developing an in vitro organ-on-chip system to model. The first step of this journey is to establish brain organoids that incorporate microglia, the brain-resident macrophages. Following ethical approval, I expanded hESC and iPSC lines, and I am now differentiating them into neural progenitors while also generating “factories” of primitive macrophage progenitors. These two precursor populations are then co-cultured to produce, after 30 days of differentiation, a neuroimmune forebrain organoid.

Once the SOP for brain organoid differentiation is fully defined, the next phase will involve embedding the organoids within tuned, animal-free hydrogels that recapitulate key parameters of the brain extracellular matrix. The final step will be to integrate these healthy, ECM-embedded organoids into the MIVO microfluidic device to establish a dynamic platform for studying early neuroimmune alterations during metastasis.

Impact of macrophage aging on tumor cell and extracellular matrix interactions – Maria Sanchez-Blazquez

To better understand how aging impacts macrophage cell biology, I am characterizing primary macrophages derived from aged (>60 years) and young (<35 years) healthy donors. As an initial step, I assessed biological age relative to chronological age by measuring the telomere length of differentiated macrophages. Functional characterization has focused on investigating age-related macrophage efferocytic capacity, revealing that aged macrophages present reduced capacity to engulf apoptotic cells.

I have established flow cytometry panels in order to profile macrophage phenotype based on expression of surface markers and secreted proteins. Currently, I am optimizing protocols to evaluate age-associated changes in macrophage chemotaxis using transwell migration assay, as well as matrix metalloprotease activity through gelatine zymography.

Next steps will involve 2D and 3D co-culture systems to investigate the aging effect on macrophage and tumor cell interactions.

Characterisation of macrophage metabolism and ageing in the brain metastatic microenvironment of neuroblastoma in response to therapy – Pierluca Cancellieri

My PhD focuses on understanding how neuroblastoma interacts with immune cells during early brain invasion using advanced 3D biomaterial models. So far, I have successfully characterized the mechanical properties of methacrylated hyaluronic acid (MeHA) hydrogels and optimized their stiffness to approximate brain-like mechanics. I established 2D neuroblastoma cell cultures and plan to evaluated ECM-dependent adhesion using multiple coatings. In parallel, I developed 3D MeHA–encapsulated neuroblastoma culture and acquired high-resolution confocal datasets to assess cell viability and morphology.

My next steps include optimizing immune cell (microglia and macrophage) incorporation into the hydrogel to model tumour–immune crosstalk during brain metastasis. I will perform metabolic profiling, immune-phenotyping, and drug-response assays within the 3D model. Ultimately, I aim to identify macrophage-targetable vulnerabilities that could impair neuroblastoma invasion and survival in the brain microenvironment.

Integrated Multi-Omics Approach to Immunoprofiling in Metastatic Tumours – Jane Mwangi

This project focuses on understanding why immunotherapies such as immune checkpoint inhibitors show limited effectiveness in metastatic prostate cancer. Current analyses highlight the dominant role of an immunosuppressive tumour microenvironment, particularly tumour-associated macrophages (TAMs), which restrict T-cell activity and promote immune escape. In prostate, aging compounds this suppression through immunosenescence, yet the molecular links between age, macrophage plasticity, and metastasis remain unclear.

To address this, I am consolidating publicly available single-cell, bulk, and spatial RNA-seq datasets from metastatic tumours, with an emphasis on prostate cancer, to build an integrated multi-omics framework. Single-cell data will enable the identification of macrophage states and differentiation pathways; bulk RNA-seq will characterize patient-level immune composition and age-related transcriptional changes; and spatial transcriptomics will reveal the physical architecture of immune and stromal interactions within metastatic niches.

The next steps involve applying reference-based deconvolution to quantify immune infiltrates, sub-typing macrophage populations across metastatic sites, and constructing regulatory networks that link cellular states to immunotherapy resistance. These workflows will be developed as scalable analysis pipelines, with the goal of extending them to breast cancer and neuroblastoma datasets across the Mac4Me consortium.

Understanding public perceptions of metastatic breast cancer (mBC) research – Aina Amat

My doctoral thesis focuses on science communication research, specifically examining how health research related to cancer and metastasis is communicated to the public and how this influences their behaviour and understanding. The aim is to identify the communication needs and potential knowledge gaps of the general population regarding mBC research, and to find ways to address these. To this end, I am currently designing a survey targeting the general adult population of Spain. In order to design this survey and ensure its usefulness and accuracy, I am organising focus groups with relevant stakeholders, including patients, relatives of patients, patient advocates, researchers, clinicians, healthcare professionals, and representatives from the pharmaceutical industry. These discussions will begin in January. The survey will also be revised by a patient advisory committee in Ireland.