Watch This Space
The power of genetic analysis is undisputed – but relying on sequence information alone means losing critical information embedded in the tumor microenvironment. Here, we discuss spatial biology approaches with Carlo Bifulco, CMO of Providence Genomics and Director of Translational Molecular Pathology at the Earle A. Chiles Research Institute, Portland, Oregon, USA…
sponsored by Lunaphore Technologies
How did you get involved in spatial biology?
It began before immuno-oncology was widely recognized, when we learned, thanks to the pioneering work of INSERM’s Jérôme Galon, that the quantification of T cells in the tumor microenvironment (TME) could predict clinical outcomes in colon cancer patients. That opened my eyes to the importance of the host-tumor interaction and I realized that the next logical step would involve multiplex immunohistochemistry/ immunofluorescence biomarkers (mIHC/ IF). Thereafter, I was fortunate to work on multiplexed approaches with Bernard Fox, who leads a team of immunologists at the Providence Cancer Institute. We were among the first to demonstrate the advantages of mIHC/IF for gaining insights into tumor biology and predicting patient outcomes.
How might spatial biology advance cancer pathology and immunology?
The host-tumor struggle plays out in the TME, but conventional analytic approaches such as tumor sequencing cannot provide a full representation of the TME – only spatial biology can do that. Indeed, spatial approaches are essential to understanding molecular interactions in the 3D space of the TME. Furthermore, spatial biology can support research from early biomarker discovery to late-stage translational research and therapy development. Companion diagnostics developed with the assistance of spatial biology will have more precise directionality than current biomarkers such as PD-L1 IHC. Also, I expect spatial approaches to guide the development of novel, rational therapy combinations in oncology. Importantly, spatial biology will provide much-needed clarity to immuno-oncology, where our current understanding of therapeutic mechanisms of action is still imperfect.
Spatial biology will also benefit from combination with other approaches. For example, mapping spatial biology data to single cell RNASeq data can support the early stages of therapy development by providing us with deep insights into the mechanisms that underlie patterns of host-tumor interactions in the TME. In brief, spatial approaches may enable us to unmask underappreciated aspects of TME biology, improving current therapeutic approaches and suggesting better immuno-oncology strategies.
What hinders broad adoption of spatial biology solutions?
The key issue is one of reproducibility. This needs to be addressed at every step in the process, from antigen retrieval/unmasking and tissue handling to the final pathological interpretation. This is essential to generate adequately reproducible data, without which we cannot translate discoveries into new therapies and diagnostics. Another key need is to develop a stack which is multilayered, not confined to a single layer – a reproducible, vertical solution.
Finally, the practicality of spatial biology needs to improve significantly; it is still very labor-intensive. And, because spatial biology generates very large datasets, it requires analytical methods that are both user-friendly and suitable for big data. In summary, spatial biology must become more reproducible and easier to perform if it is to be broadly adopted.
How do you envision the future of spatial biology?
I foresee a situation in which investigators can refer to a catalogue of biomarkers, choose the ones that best apply to a particular tissue or TME, and employ them via a simple protocol that generates reliable data. This ease of use will be maintained throughout the experimental pathway, from antigen retrieval and tissue staining to statistical analysis of the results.
What key messages regarding spatial biology would you like to convey?
To pathologists, I would say: watch this space! Pay attention to the rapidly evolving field of spatial biology and get involved if you can. It has potential beyond research and, I believe, will soon provide us with improved diagnostic tools that will lead to better clinical decisions. As pathologists, you will be the leaders of this change, so you should become familiar with spatial approaches as soon as you can. And remember – oncology will benefit from greater involvement with the pathologist community because interpreting spatial biology data requires morphological expertise. Without such expertise, patients will suffer worse outcomes; that’s why it is essential for pathologists to more deeply engage with this field to the benefit of all.
