NanoString sat down with McGarry Houghton, M.D., Associate Member of the Clinical Research and Human Biology Divisions at Fred Hutch Cancer Research Center, to discuss how his lab is using 3D Biology™ Technology to advance understanding of the lung tumor microenvironment and phenotypic differences in immune response.
NanoString (NS): Could you please give an overview of your work and how you became involved with NanoString Technologies?
McGarry Houghton (MH): We are interested in understanding the complexity of immune cell composition and function within the lung tumor microenvironment. Most of our research approach has been to drive the answers to two questions: what is the ideology of anti-PD-1 treatment failures, and can you gather new information to improve the response rate for these drugs up from 20% of patients to help that other 80% of patients.
I became familiar with the NanoString platform though a collaboration and immediately saw that it could augment my ongoing projects. The most important aspect of the platform is the ability to use it in analysis of FFPE specimens. In translational research, you can go to great lengths like we’ve done to get fresh tissue specimens, but you exhaust them quickly. The ability to do the NanoString assay on FFPE tissues is extremely important. If your goal is to ultimately get your findings into the clinical arena that means FFPE. For us, the ability to access so much data from one curl is what drove us to engage in using the technology.
NS: What did you hope to discover by performing mutational, gene, and protein expression profiling?
MH: We are trying to determine if specific oncogenic drivers or pathway hyperactivity can dictate the immune response in lung cancer.
NS: How do you use 3D Biology Technology, and what techniques did it replace?
MH: We use the 3D Biology concept to obtain multiple parameters of data on the same cases. We haven’t necessarily replaced other technologies but instead added to the total amount of data available to interrogate on a given case. With the gene expression from the PanCancer Pathways Panel combined with the phosphoprotein data, you can cluster your specimen in multi-analytical parameters to find insights and identify genes that may be driving tumor biology that you otherwise wouldn’t see. Looking at the multi parametric strategy will identify aspects of tumor pathobiology you just will never see using a single assay.
NS: Lung tissue and tumor samples are difficult to obtain. How much sample are you usually working with? How much is needed to run Vantage 3D™ assays?
MH: Currently, we are using a multiplexed IHC panel and several NanoString assays. We can do all of this from an FFPE block. A major advantage to the Nanostring platform is being able to perform analysis from an FFPE curl and to use that for all the multi-analyte assays. When you’re talking about research samples from patients that are getting novel therapies you need platforms that can use very small amounts of tissue, and all Nanostring analysis can be performed on a curl or on one to two slides. We’ve added several NanoString panels to our ongoing study that has enhanced the biological insight. We’ve used the nCounter® Vantage 3D™ SNV Solid Tumor Panel, the PanCancer Immune Profiling and PanCancer Pathways panels, which are gene expression panels, and then added the protein and phosphoprotein analysis with the nCounter® Vantage 3D™ Protein Solid Tumor Panel.
NS: What preliminary results have you obtained from these studies?
MH: The immune cell content and function is quite diverse in lung cancer. There are numerous factors that influence this. Exome sequencing can be a problem in these immune rich specimens, but we were able to use the SNV panel to quite easily see mutations despite the immune rich nature. By looking at gene expression, protein, and mutational data holistically, we have identified novel subgroups of immune activated and immune exhausted phenotypes in our cases.
NS: How does this new data further lung cancer research?
MH: It provides a future opportunity to identify rationale secondary therapeutic targets that could be used to improve response rates to existing immune based therapies.
NS: What are your next steps in your research?
MH: To perform similar research using multi-analyte assays on biopsy specimens obtained prior to the initiation of immune checkpoint inhibitor therapy and to stratify the results by treatment outcomes.
To hear more about McGarry’s study and view the results, register for the on-demand webinar here.
To learn more about 3D Biology Technology, click here.
FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.