What is a CyTOF machine? Why is it important for cancer research?

What is a CyTOF machine? Why is it important for cancer research?

What is a CyTOF machine? Why is it important for cancer research? 150 150 Joedance Film Festival



Al McMillian, Board Chair of Joedance Film Festival, seeing the CyTOF machine up close while touring the pediatric cancer research lab.png

Warning: Unlike the posts written (primarily) by David, this post might come across as dry, boring, lifeless, and technical.

However, that doesn’t make it any less important to read. To make this as painless as possible, I will try and avoid my usual problem of getting too in the weeds.

A question that seems to be asked amongst both our many supporters, friends, and board members is why was the hospital so excited about being able to purchase a CyTOF machine?

What does it do?

How is it used to better research cancer?

All completely valid questions; one that has many answers. We will focus on just one aspect of this discussion.

One area of cancer research that has been gaining tremendous focus and traction in the past few decades is the role of the tumor microenvironment in cancer progression, and how the immune system is involved in this environment.

Instead of thinking of cancer as a bunch of cells that have gone rogue, many scientists and doctors have started to view it more as an organ, with a bunch of different cells working together to provide a space for cancer cells to be able to freely and rapidly grow and metastasize.

As stated above, one major focus of this environment is immune cells that comprise this space (note: the immune system and its functions are incredibly complex, we will not address that in detail here for the sake of everyone’s sanity). In response to the immune systems’ role in cancer, immunotherapies have been an increasingly growing field for new therapies for cancers. So not only does the immune system play an important role in cancer pathology, but it also is an increasing target for therapeutics.

So, the question now is, how do scientists study the immune system and its role in cancer?

One main tool that is used is a process called flow cytometry. This is a device that is used to sort cells based, most commonly, by tagging and separating cells using fluorescently tagged antibodies specific to cell antigens. Speaking from experience I can tell you that there are some difficulties and limitations that come with this process. A major one is the limitation of the number fluorescent antibodies that can be used to help identify cell populations, generally maxing out at about 15 or so antibodies. The moreantibodies you include in your panel, the more likely you are to have less defined populations due to a “bleeding” effect, where fluorescent antibodies of similar wavelengths create less defined populations.

As such, fluorescence mediated flow cytometry has limitations in the specificity and number of immune cell populations seen in the tumor microenvironment.

This is where the CyTOF machine improves our ability to study the immune system in cancer.

Instead of using fluorescent antibodies, this flow cytometry machine uses antibodies tagged with heavy metal isotopes and utilizes a process like mass spectrometry to provide analysis of single cells based on the ions that are collected, and populations can be identified. Furthermore, due to using mass spectrometry, which measures mass-to-charge ratio of ions, the number of antibodies that can be included in the analysis easily exceeds the number used in fluorescent flow cytometry, estimated to be more than 100 antibodies. Thus, CyTOF analysis can provide for greater sensitivity for the detection of immune cell populations, a greater number of parameters to further identify and define cell populations, and it eliminates the “bleeding” effect that introduces errors when using fluorescent antibodies.

In summary, the CyTOF machine allows scientists to identify specific and unique immune cell populations present in the tumor microenvironment. The identification of these populations will increase our understanding of how the immune system provides support and protection for cancer to progress and metastasize, and additionally provide targets that can be isolated for the development of new therapies and treatments.


Al McMillian, Board Chair of Joedance Film Festival, seeing the CyTOF machine up close while touring the pediatric cancer research lab (1).png

Citations

Cheung, R. K., & Utz, P. J. (2011). Screening: CyTOF-the next generation of cell detection.Nature reviews. Rheumatology,7(9), 502–503. https://doi.org/10.1038/nrrheum.2011.110

Bendall, S., Nolan, G. From single cells to deep phenotypes in cancer. Nat Biotechnol 30, 639–647 (2012). https://doi.org/10.1038/nbt.2283

Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., Coussens, L. M., Gabrilovich, D. I., Ostrand-Rosenberg, S., Hedrick, C. C., Vonderheide, R. H., Pittet, M. J., Jain, R. K., Zou, W., Howcroft, T. K., Woodhouse, E. C., Weinberg, R. A., & Krummel, M. F. (2018). Understanding the tumor immune microenvironment (TIME) for effective therapy. Nature medicine,24(5), 541–550. https://doi.org/10.1038/s41591-018-0014-x

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013