Discussing current cancer biomarkers at CCBIO’s 12th Annual Symposium

This was the final symposium during CCBIO’s 10-year period as a Centre of Excellence (CoE), however not the last. The first symposium of CCBIO’s continuation phase (CCBIO 2.0) is planned for May 13-14, 2025, and dates for the coming 10 years are already booked and plotted in CCBIO’s calendar. Save all the dates for later!

As is CCBIO’s tradition, the scientific program covered a broad range of current topics within cancer biomarkers, with many renowned international speakers, among them Raza Ali (“Charting the intact breast tumour microenvironment”), Frances Balkwill (“Modelling and targeting the tumour microenvironment of high-grade serous ovarian cancer”), Ian Mills (“Spatial approaches and imaging to improve prostate cancer stratification”, Linda Lindstrøm (“Insights into the heterogeneity of ER-positive breast cancer - long-term risk, endocrine treatment benefit and intra-tumor heterogeneity”), Randy Watnick (“Discovery of a novel signaling pathway mediating immunosuppression in solid tumors”), Göran Jönsson (“Understanding response to immune checkpoint blockade in melanoma”), Anna Vähärautio (“Tracing back primed resistance in cancer”), Patrick Micke (“Functional diagnostics for optimised lung cancer therapy”), and Rolf Brekken (“Phosphatidylserine - a marker of the tumor microenvironment and much more”). See the full program here.

The challenges of translating tissue imaging results

One of the current ‘hot topics’, and a strategic field for CCBIO, relates to imaging mass cytometry – and was particularly covered in the keynote presentation by Raza Ali from Cambridge University. We had a chat afterwards with Dr. Ali on the challenges of translating imaging discoveries to treatment for the patients, a question the audience was particularly concerned with. 

“I think there are many challenges,” Raza Ali explains. “Biomarkers from tissue-based imaging will necessarily have to get into a pathology setting. Currently, biomarkers are evaluated by pathologists by eye. We as academics tend to use computer vision to quantify biomarkers. To give an example, PDL1 is still interpreted manually. Translating these complex tissue-based imaging biomarkers to the clinic means we need to come to a place where we either modify what we do in the clinical setting, or we find some sort of suitable surrogate which can be evaluated by the pathologists manually. And both of those have their own challenges. Changing what we currently do, in a widespread way, I think is going to need new solutions. We are still far from that. I’m not even sure it’s necessarily the best thing to do. I hope that there will be an interface between increasingly sophisticated computer vision widely used in pathology labs with digital pathology, and the sort of approaches that we develop. We expect to find a way somewhere in between. There are loads of challenges.”

When considering the future of imaging in cancer research, Dr. Ali finds the future hard to predict, as well as the role of AI. 

“I'm always hesitant in predicting the future because it's very non-linear,” he explains. “You need just a few breakthroughs to completely change the field. I think we’re very early in the space of analyzing these sort of high-content tissue images. And we haven't really done it in a very sophisticated way. One of the things that we’re struggling with is how to effectively represent the data. If you characterize a discrete number of cell phenotypes, let's say 40, which is pretty low and it still doesn't cover the whole, and you say, I want to understand all the different cell interactions in the tumour. Well, all of those 40 phenotypes can interact with all the other 40 phenotypes. So, you end up with a very long list of potential interactions. Dealing with those sorts of data effectively is a challenge. And that's one of the places where AI may help us, to compress those data in a way which is efficient. The other big possible promise for AI is to learn directly from these sorts of multidimensional images, features that are predictive of the clinical outcome, but that has huge challenges because you need very large data sets, you need true validation data sets, and you need to ensure that what you're detecting is interpretable and is relevant biologically, and to avoid finding features which are artefacts of the method. The other spaces that continue to evolve are three-dimensional imaging and mapping, genomics and proteomics. Mapping genomic clones to tissues and mutational profiles to tissues I think will become more and more widespread. I'm uncertain whether it will transform our understanding of cancer, but it has a lot of potential,” Dr. Ali concludes.

Overcoming treatment-resistant cancer cells

Keynote speaker on day 2, Göran Jönsson from Lund University Cancer Centre, showed that although recent breakthroughs in the management of melanomas take advantage of the power of the immune system to achieve previously unattainable control of the disease, the current immunotherapies do have limitations. We need more knowledge on how immunotherapy affects the tumor, the surrounding stroma and the anti-tumor immune response. Jönsson presented intriguing work from his group, showing that tertiary lymphoid structures (TLS) are important for the anti-melanoma immune response. Resolving the functionality of TLS’ may therefore help us find new immunotherapeutic options, ultimately overcoming therapy-resistance. 

Treatment resistance was also discussed by Anna Vähärautio from the University of Helsinki. Her group addresses the challenge by developing ReSisTrace, a methodology that utilizes shared transcriptomic features of sister cells to predict the transcriptomic states priming treatment resistance in cancer. Initially, the method was applied to reveal pre-existing resistant cell states against chemotherapy, targeted therapy or innate immunity in a high-grade serous ovarian cancer cell line. In ReSisTrace, cancer cells are labelled uniquely with genetic barcodes and allowed to divide once so that each sister cell pair can be identified based on a shared barcode. Then single cell transcriptomes are analyzed from half of the cells before the treatment, while treating the other half. Finally, analysis of the surviving cells enables the identification of the resistant lineages and tracing back their pre-resistant states via the sister cells analyzed prior to the treatment. Now, they have expanded the method to a patient derived ovarian cancer organoid model. Even in this more heterogeneous and challenging context, they were able to identify a pre-existing chemoresistant state, and successfully target it with a pre-sensitizing therapy, thus suggesting broad applicability of the method.

Global perspectives on cancer

One session, chaired by Roger Strand, was dedicated to global perspectives on cancer, comparing the global north to the global south. The session was initiated by Kjell-Arne Johansson from the Bergen Center for Ethics and Priority Setting (BCEPS), with the talk “Prioritizing Cancer Care in Low- and Middle-Income Countries (LMICs): Addressing the Humanitarian Crisis and Competing Health Priorities”, and by CCBIO’s Dana Costea who has several collaborations with the global south and who reflected on cancer research in the different global regions. A panel conversation with the two as well as with John Cairns, London and CCBIO and guest researcher Dr. Karpal Singh, Dar es Salaam touched upon the huge differences between the regions. Dr. Singh described challenges such as superstition and lack of knowledge among the patients, economic and political challenges and limited resources on a whole different level than experienced by the global north, and the fact that most of the patients come too late to the medical facilities. And, as showed by Johansson, there is an urgent need to balance competing health priorities while working for fair access to cancer care in the global south. The economist John Cairns pointed out the need to look at it more broadly than what is necessary in the north, and include resources, politics and cancer prevention. As the situation is today, institutional level collaborations between the north and south are the best way for us to contribute.

Maintaining and building on a strong network

Prior to the symposium, the CCBIO Scientific Advisory Board (SAB) had its closing meeting with the CCBIO management after its 10 years of service. The SAB members, Professors Carl-Henrik Heldin, Bruce Zetter and Ate van der Zee, are all internationally leading researchers in CCBIO-relevant fields. 

SAB chair Carl-Henrik Heldin, professor in molecular cell biology at Uppsala University, and former chairman of the Nobel Foundation, finds the symposium to be a big success through CCBIO’s 10 years as a Centre of Excellence. “I think it would be a very good idea to continue it,” he says, and continues: “I think – from the university perspective – this should have high priority, because through the Centre of Excellence CCBIO, the university gained a lot.”

Full interview with Carl-Henrik Heldin will soon be available in a separate news story on CCBIO’s current status and future.

Showcasing young researchers

As in previous years, CCBIO facilitated speedtalks and poster sessions for young cancer researchers to show their research and provide presentation experience. 13 speedtalks and 43 posters highlighted a wide range of the work of the young researchers. The audience had the opportunity to vote for the two best presenters of each session. Congratulation to:

• Lorena Larios Salazar in Dana Costea’s group at CCBIO, who won both a speedtalk and a poster award for the work Development of patient-derived 3D multicellular models as prediction tools for head and neck cancer therapy - testing the ‘clinical trials in a dish’ (CTiD) concept
• Eric Holt in Nils Halberg’s group at the UiB, with a speedtalk prize for the work The pancreas remembers: Epigenetic memory of obesity as subtle, coordinated changes in promoter accessibility that disagree with gene expression and histone acetylation changes
• Inês Ferreira in Carina Strell’s group at CCBIO, with a poster award for the work Nerve innervation in NSCLC
• Gina Nyhus Stangeland in Emmet McCormack’s group at CCBIO, with a poster award for the work Establishment of Patient-Derived 3D Ovarian Cancer Models: Using Peritoneum to Mimic the Extracellular Matrix
• Ariell Thale Toftesund Longva in Nils Halberg’s group at the UiB, with a poster prize for the work Alternate Day Fasting Changes the Immunological Landscape of Pancreatic Adenocarcinoma

The importance of patient and public involvement

CCBIO has to an increasing degree brought the patient perspective into its activities, and the last couple of years, a patient and public representative was invited to the annual symposium as audience, Jeanette Hoel, currently collaborating with CCBIO’s Co-Director Line Bjørge in a research project as the patient representative. Jeanette finds it very useful to be at the symposium, although it is a conference aimed at medical professionals.

“I certainly understand how much cancer research there actually is, that is never brought to the public attention,” Jeanette explains. “I think the patient organizations should have much more knowledge of this,” she continues. “I would like to see the patient organizations getting informed of this research activity and convey it to their members and to other affected people.”

Full interview will soon be available in separate article. 

CCBIO – into the ‘great wide open’

The CCBIO Director Lars A. Akslen finds that this year’s symposium has continued to focus on timely and ‘hot’ topics – such as single-cell analytics technology and high-dimensional tissue imaging, relevant for mechanistic studies and also closer to the clinic, for example in mapping of the tumor immune microenvironment and response predictors for immunotherapy. 

“This has been yet another vibrant and very stimulating meeting with a lot to learn – and multiple interactions with young and more senior colleagues. I think these annual meetings have become extremely important for the local cancer research community, but certainly with a national and international participation and perspective as well. It is very motivating to already start the planning for next year’s gathering – when we enter the CCBIO 2.0 phase and continue into the future. It is time to move ‘into the great wide open’.