In a paper published in JAMA Oncology, researchers from Johns Hopkins University conducted a systematic review to compare the efficacy of different biomarker modalities in predicting response to PD-1/PD-L1 checkpoint blockade.
The researchers found that multiplex immunohistochemistry/immunofluorescence (mIHC/IF) performed significantly higher in measures of diagnostic accuracy for predicting anti-PD-1/PD-L1 therapy when compared to other techniques, such as PD-L1 IHC, tumor mutational burden (TMB), and gene expression profiling.
We explored these findings in-depth in a webinar featuring the first author of the paper, Steve Lu, an MD/PhD candidate from Johns Hopkins University and Dr. Cliff Hoyt, VP of Translational and Scientific Affairs at Akoya Biosciences.
Cancer immunotherapy and the tumor microenvironment
In recent years, we’ve seen lasting benefits resulting from cancer immunotherapies, but many patients don’t respond to treatment. Effectively classifying patient populations is important to ensure the right patients receive the right treatment.
“The goal [for] us in the biomarker space is to develop tests that help further stratify patients into subclasses, within which you get higher response rates,” said Hoyt.
The prevailing thinking, he added, is that the answers lie in the tumor microenvironment (TME). Cancer cell behavior is a function of what is happening in their surrounding environment, including the signals they receive from other cells.
The only practical way to observe the TME is to stain tissue sections with multiple markers and image. Multiplex staining offers more information and context about the microenvironment compared to single stain methods, said Hoyt. You can distinguish between cell types, observe their functional states, and identify any checkpoint-related proteins present.
Multiplex IF also supports our understanding of the cell-to-cell biology driving disease progression. With spatial context, it’s possible to unlock cellular mechanisms behind disease and discover new therapeutic targets. This can be used in trials to confirm drug mechanism of action and identify patient cohorts enriched for response – especially helpful for pharmaceutical companies in order to develop effective therapies.
At Akoya, our goal is to provide platforms that support the biomarker development continuum from discovery to clinical commercialization. Hoyt emphasized that requirements for these platforms change as you travel along the continuum. Research in the discovery phase requires platforms like CODEX® , which have high multiplexing capabilities to support biomarker discovery. Simplicity is key at the clinical end – imaging systems like the Vectra® and Mantra® offer lower-plex but higher throughput.