The ability to customize treatment demands comprehensive knowledge about the nuances of each individual’s disease. With CyTOF technology, we will be able to explore cell populations and biological systems with unprecedented depth and take our outstanding treatment modalities to new levels of excellence in the pursuit of superior outcomes for every patient.
Over the past decades, our understanding of myeloma stem cell biology and immunology has been greatly enhanced by improvements in single cell analysis technologies that have made it possible to quantify the expression of multiple genes on the surface of individual cells and determine the cellular subtypes of the immune system. We have been able to determine what makes cancerous myeloma cells different from normal cells and use this information to design optimal treatments and stimulate the immune system to fight cancer.
Fluorescence-activated cell sorting, or flow cytometry, has been the standard technique for recognizing the cellular subtypes of the immune system for many years. However, this technique is limited by the number of fluorescent tags that can be used to identify cells, and therefore not all of the integral components of the immune system can be identified simultaneously. Typically up to eight markers can be used in this type of cell sorting.
To combat this limitation, a new technology has been developed that can detect up to 35 markers at the same time allowing a more detailed examination of the many cell types present in the bone marrow and their interactions. The technology couples flow cytometry with time-of-flight mass spectrometry, and is known as CyTOF (Cytometry by Time of Flight). With CyTOF, many more of the immune cell subtypes can be identified simultaneously. This will allow us to be more precise with our treatments.
How can CyTOF translate to improved patient care?
- Our researchers will be able to study how different immune populations in the bone marrow interact with myeloma cells and influence tumor growth and survival.
- CyTOF can study the function of the immune system at a single cell level, enabling us to further develop immune therapy treatment options.
- We will gain a better understanding of the features of the cells that cause myeloma and related diseases by identifying signaling pathways that we can then target with specific therapies for improved outcomes with minimal toxicities.
- CyTOF and its analytic tools will help us evaluate and interpret disease evolution in serial patient samples and response to specific therapies.
- We will be able to expand serial patient samples into larger groups of disease-resistant cell populations and cell signaling pathways that predict the risk of relapse.
Immune cells of the bone marrow
Bone marrow is the spongy tissue inside our bones that produces blood cells – red blood cells, platelets, and white blood cells.
White blood cells help the body fight against infection. There are many different types of white blood cells, including lymphocytes, neutrophils, and monocytes. They fight against invading bacteria, viruses, or fungi to help destroy infection.
Three major types of lymphocytes play an important role in the immune system.
B-lymphocytes (B-cells) originate in the bone marrow. They make proteins called antibodies which attach onto the surface of infection-causing microbes. Generally, these are Y or T shaped. Each type of antibody reacts to different microbes by sticking to molecules, called antigens, which sit on the surface of the microbe. It is this antibody-antigen binding that triggers B-cells to grow and produce more antibodies, which fight infection.
T-lymphocytes (T-cells) mature in the thymus, which is a small organ in the upper chest, just behind the sternum (breastbone). T-cells help B-cells make antibodies against invading bacteria, viruses, or other microbes. Unlike B-cells, T-cells can produce chemicals that kill infected cells, after binding to the antigen on the surface of the infected cell.
T regulatory cells suppress immune responses of other cells. This is an important “self-check” built into the immune system to prevent excessive reactions.
Natural killer (NK) cells are a type of lymphocyte that directly attacks cells which have been infected by a virus.