You’ve been an early adopter of multiplex immunohistochemistry/immunofluorescence (IHC/IF) technologies. Why is multiplex IHC/IF an important tool for immunopathology?
Multiplex IHC gives you the opportunity to actually stain more colors. You can talk about CODEX, or MIBI or CyTOF. People are doing 50 or 60 colors. As a translational group, we are more interested in how to do this in a fashion that can be for clinical tests, or at least for clinical trial monitoring. We care about the costs and the turnaround time. You can spend a lot of money to run one sample, generate big data and analyze it for a long time. There are groups that focus on this, but ours focuses more on the translational part.
The key component is how to make the cost bearable and have an acceptable turnaround time in a translational or clinical setting.
Our focus is the clinical kinds of tests in the market, for example as easy as PD-L1, right? It would be good to have PD-L1 core staining with a tumor marker or immune marker, or even with a macrophage marker. Multiplex IHC definitely gives you a lot of advantages to be able to accurately quantitate the PD-L1 positivity. This becomes very important, because if you want to give the patient anti-PD-1/PD-L1, and other immunotherapies, you obviously need more markers to accurately quantitate this.
Even in a conventional situation, there are already pathologists that, in the past one or two decades, stain two different markers in sequential sections and, in their mind, try to reconstruct it. It’s a no-brainer to use this technology now, especially the Opal/Vectra. It’s been there for years. The recognition, the acceptance levels are high.
It’s also a no-brainer that you want to study more lineage markers. For example, I mean, everybody knows Immunoscore, from HalioDx. It’s very famous. CD3, CD8 – people believe that it is definitely important to score these. And it can also potentially be applied in the clinical setting, for many, many different situations. Why aren’t people doing it? I think the key bottleneck is that you do not want to spend too much tissue on something, and also if the quantification is done by a pathologist, you don’t want to spend more of their time.
But with multiplex IHC, once you optimize it, you have a panel. It can be automated or at least very high throughput. For example, if you’re interested in PD-L1, you stain PD-L1 with some other markers to know if it’s a PD-L1 colocalization. There’s no harm in putting CD3 and CD8 in the patient panel; the readout is almost simultaneous. Then you know the CD3/CD8 quantification, or even spatial information for this patient. All this looks like very easy, basic stuff, but at the translational and clinical level, you need a lot of people and critical mass to push this and then make this something that people believe can be executed in a larger population.