Spatial Biology: Transforming Immuno-Oncology Research

An interview with Paolo A. Ascierto

Can you give me an overview of spatial biology? 
Spatial biology is the study of tissue within a 2D or 3D context. In particular, we’re interested in investigating the interaction between different cells within the tumor microenvironment (TME). Such interaction is important not only from a histological point of view but also from a molecular perspective, because it is possible to look at the distance of specific cells, understand the expression of some molecules, and search for the presence of cytokines. For immuno-oncologists, such knowledge is crucial to understanding the process that underlies the immune response to treatment.

How can spatial biology support immuno-oncology research? 
We have seen exceptional growth in the field over the years – and now we’re looking toward uncovering a set of biomarkers to gain a better understanding of primary resistance. At the moment, we don’t have many biomarkers; PD-1 expression is used in lung cancer, but it is useless in cancers such as melanoma. There has been an increased interest in tumor mutational burden, but it’s not used in clinical practice. We have also seen the importance of microsatellite instability markers. With the Immunoscore, we’re seeing that the immunocontext is just as important.

Clinicians want to know which patients will respond to high-cost treatments before prescribing them but, without any biomarkers, that’s difficult. I believe that specific knowledge of the spatial relationship between immune system cells and tumor cells will be important for finding prognostic biomarkers – not only because spatial biology can give us a better understanding of the mechanism of resistance, but also because it might be important for finding additional drug compounds that could help patients.

Spatial biology is a growing field. How could it affect the future of melanoma research? 
At the moment, there is no biomarker for melanoma patients. We don’t know which patients might benefit from anti-PD-1 or anti-PD-L1 therapy (or a combination). Using the TME immunocontext, spatial biology can help clinicians identify those patients who may be more likely to respond to a particular treatment.

We can also treat patients with second-line therapies; if a patient fails first-line treatment, we can look at the progression of the TME and see if there’s something that will help us to select the next best treatment.

What could shorten spatial biology’s journey into the mainstream? 
By using new technologies in the early phase of development, we are more likely to find a biomarker that is correlated with treatment. Introducing spatial biology in phase I trials is important because we can investigate direct correlation without complications and, sometimes, with increased safety. If we can find a biomarker that could be useful for clinical application, then the technique could be used in phase III trials to confirm what we have seen in the earlier phases of development.

What are the main barriers to spatial biology adoption? 
Validation and reproducibility of analysis are two critical points. We need to collect data on a large cohort of patients to validate the technology. After that, I am convinced that more widespread adoption is just a matter of time. Once we have the data, it is relatively easy to move forward with validation and demonstrate spatial biology as a reproducible technology.

What needs to be done to encourage the adoption of spatial biology? 
I believe it’s important for researchers who are experienced in spatial biology to model leadership in the field and increase training of the next generation. It’s also important to organize a network to enable a group of experts to discuss data, slides, samples, the meaning of the interactions between cells, and their correlation with outcomes. Furthermore, there is a significant need for collaboration between industry and academia. A focus on this latter point, in particular, would help speed up the process of translational research and, in turn, clinical application.

Paolo A. Ascierto is Director of the Department of Melanoma, Cancer Immunotherapy, and Development Therapeutics at the National Tumor Institute, Naples, Italy

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