At KI Science Park’s Science After Work, Oct 8, researchers and industry met to discuss a practical path into spatial biology and biomarker discovery, why it matters, and how a new kit aims to make it easier.
High‑grade serous ovarian cancer remains one of the most challenging tumours in women’s health, often diagnosed late, biologically diverse, and not always responsive to immunotherapy. As Cecilia Lindskog (Associate Professor, Uppsala University; Head of the Tissue Atlas at the Human Protein Atlas) put it:
“In my lab we’re studying the tumor microenvironment of high‑grade serous ovarian cancer, the most common and aggressive gynecological malignancy. Symptoms are diffuse, leading to late diagnosis; the tumors are heterogeneous and often respond unpredictably to immunotherapy. We aim to better stratify patients, especially those at higher risk of relapse.”
That need, to map the spatial location of proteins in cells, is why spatial proteomics was named Nature Methods “Method of the Year” for 2024. In plain terms, spatial proteomics lets scientists map where proteins sit inside tissues, revealing how immune cells, tumour cells, and stromal cells interact in situ. It’s the difference between a list of parts and a working schematic, essential for precision medicine.
The Human Protein Atlas: a map and a toolbox
The Human Protein Atlas (HPA) is one of the world’s largest open resources for where proteins are found in human cells and tissues. Lindskog leads the Tissue Atlas effort and was recently awarded the Erik K. Fernström Prize for Young Researchers for systems‑biology work that blends single‑cell analysis, spatial proteomics, advanced bioinformatics, automated image analysis, and machine learning.
HPA isn’t just a map; it’s a living toolbox for the community. As Catrin Siöberg (Head of R&D, Atlas Antibodies) explained:
“Atlas Antibodies was founded by researchers behind the Human Protein Atlas and turns twenty next year. We supply highly validated antibodies for tissue and cell analysis, more than 23,000 primaries, and ship tens of thousands of vials annually. The HPA remains an active, open access resource that our company both draws on and supports.”
Why multiplex imaging is hard, and how amplification helps
Seeing many proteins in the same slice of tissue (multiplex imaging) is technically tricky. Mikael Malmqvist (Principal Scientist, Atlas Antibodies) described the bottlenecks: tissue autofluorescence can bury weak signals, and methods that cycle through markers can be slow or harsh on samples. The team leans on tyramide signal amplification (TSA) to boost sensitivity:
“TSA uses HRP mediated chemistry to deposit fluorophore labeled tyramide near the antigen, creating a covalent, amplified signal. That boosts signal to noise in challenging tissues and helps you detect weaker targets.”
Cecilia added that her group’s earlier cyclic workflows could take roughly a week for 5–6 plex runs and that repeated heat steps “can affect morphology”. This is good science, but not always practical when sample quality is limited.
A kit built for routine FFPE tissue and everyday microscopes
Against that backdrop, Atlas Antibodies introduced AtlasPlex™, a ready‑to‑use kit designed to bring iterative multiplex immunohistochemistry (IHC) to routine FFPE tissue and standard fluorescence microscopes. Malmqvist summarized the approach:
“A kit that enables multiplex tissue staining using HRP labeled primary antibodies (via biotin–streptavidin), keeping TSA level amplification while avoiding harsh stripping. Between targets we quench HRP instead of stripping, preserving tissue integrity and speeding the protocol.”
In practice, AtlasPlex combines an optimized TSA system with pre‑biotinylated primary antibodies and fluorescent tyramides, so labs can detect up to five biomarkers in a single day, with ~1.5 hours per cycle. Because the kit quenches the enzyme between targets instead of stripping antibodies off the tissue, you keep morphology intact and reduce carry‑over, which is one reason runs are faster and more reproducible. Another practical perk: no host‑species restrictions on primaries, and no secondary antibodies are required.
Crucially for panel design, researchers can build custom kits by choosing from >12,000 HPA‑validated human targets, making it straightforward to tailor assays to a disease question, be it immuno‑oncology, fibrosis, or neurodegeneration.
Bringing it back to patients: ovarian cancer use case
Lindskog’s lab is already applying AtlasPlex to high‑grade serous ovarian cancer, focusing on the immune and stromal players that shape outcomes:
“Two biomarker avenues are important: early detection (often a blood-based route) and predicting relapse, prognosis, or drug resistance from tissue at surgery. To map the TME more precisely — cold, excluded, or inflamed phenotypes, we combine transcriptomics, conventional IHC, and multiplex profiling.”
“We built a TME panel for macrophages, B cells, CD8 T cells, fibroblasts, and tumor epithelial cells using Human Protein Atlas antibodies (sold by Atlas Antibodies). Conveniently, the same antibodies can be formatted for AtlasPlex, allowing a direct comparison between our cyclic workflow and AtlasPlex.”
“Fresh from the lab: we have successful AtlasPlex staining for T cells, fibroblasts, and tumor cells. Next, we’ll benchmark signal strength, background, marker overlap, and histological quality vs our cyclic method. With a fixed core panel in place, we’ll add a sixth target guided by transcriptomics and move toward quantitative image analysis and clinical relevance.”
What about tough tissues like human brain? Here, too, the team sees a role for amplification:
Mikael: “Yes—TSA helps overcome strong autofluorescence and improves signal to noise.”
Cecilia: “Human post mortem brain is variable; protein degradation and processing artifacts make it harder than fresh mouse brain. Amplified methods help, but sample quality still matters.”
Discovery today, diagnostics tomorrow
Lindskog was clear‑eyed about the road to clinical routine:
“Routine pathology largely relies on conventional IHC. It is robust and cost effective. Multiplex is powerful for discovery and panel design; once key markers are known, streamlined IHC panels can carry them into the clinic. Adoption of multiplex in routine settings is increasing but not yet universal.”
That balance of using multiplex to learn, then simplifying to scale, tracks with the broader field. With spatial proteomics now Method of the Year, and large atlas efforts accelerating, tools that make high‑quality multiplex feasible on everyday equipment can help more labs join in.
Gustav Ceder