Validation of multiplex immunofluorescence and digital image analysis for programmed death-ligand 1 expression and immune cell assessment in non-small cell lung cancer

The brilliant Stephen Hawking once said that “The universe does not behave according to our pre-conceived ideas. It continues to surprise us.” The same statement is also true for how we think of the dynamic nature of the cancer universe, in particular the complexity of the tumor immune microenvironment (TiME/TMEs)- an ever-evolving rich milieu comprising of non-malignant immune cells, fibroblasts, adipocytes, extracellular matrix components and neuronal cell types.

I’ve always been curious, with a need to be on the cutting edge of scientific innovation, so after a successful academic career I moved to the rapidly evolving world of biotech. A 15-year journey in this space ultimately led me to Ultivue, their novel InSituPlex® assay, and following advances in tissue multiplexing.

It’s clearly a very timely discussion with many recent articles reviewing the complexities of the tumor microenvironment and overall tumor heterogeneity that have been implicated in late-stage clinical failures, underscoring an urgent need for tests that accurately predict response to the growing number of available therapies.

I have learned in my career that there is a special recipe for making young companies successful. You need to have an amazing product that enables customers to accomplish their goals in a better way than their current method.

Despite advances in immunotherapy, it’s clear that only a minority of patients respond. Therapies that rely on immune activation, such as checkpoint inhibitors, have been shown to be especially difficult due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Clearly there’s much anticipation and focus on new contenders for successful combination checkpoint therapy.

GEN: If I were to design my own panel for immunofluorescence, what are the main considerations, given everything you’ve suggested during the webinar for validation? Angela: There are several things one needs to think about when you build a new panel for multiplexed immunofluorescence. You need to consider the abundance of the targets to be

Adapted from a line in “Ode to a Mouse” from fellow countryman Robert Burns, the phrase, “the best-laid plans of mice and men often go awry”, indicate that no matter how carefully a project is planned, something may still go wrong with it unfortunately speaks to the reality of clinical trials for novel therapeutics, with approximately only 11% of drugs that begin phase I clinical trials eventually being licensed.

Alfred Hitchcock once said, “The more successful the villain, the more successful the picture”, for the immunotherapy picture, that successful villain is M1 macrophages.