Applying spatial context to the cancer immunome
The immune system is naturally complex. In order to fully characterize the different immune populations, two or three markers won’t be enough, according to Dr. Villasboas. Instead, we need a series of markers that, when put together, are able to determine the role of the immune cell in the broader context of the immune microenvironment.
“Context, in immunology, is everything,” says Dr. Villasboas. The position of a cell in the tumor microenvironment can have important implications for its function and relationship with other cells. An immune cell that is in direct contact with a tumor might be providing growth factors to promote tumor growth instead of attacking it. By taking into account both the proteins expressed on the surface of the cell, but also the position of the cell in relation to the tumor and other immune cells, it is possible to study the full breadth and depth of the immune system’s complexity.
Analyzing a peripheral blood sample provides bulk data from all nucleated cells. It doesn’t tell you if a mutation or epigenetic regulation being detected is coming from the tumor compartment versus the normal immune system compartment, says Dr. Villasboas. It’s single-cell, spatial technologies that get us close to that answer.
Context, in immunology, is everything.
When you analyze tissue with single-plex IHC, you go into it with a bias, says Dr. Villasboas. You might stain for CD3 because you expect to see it expressed in T cells. While this may be valid, you also lose the opportunity to discover something unexpected. A highly multiplexed panel gives investigators the ability to find more cell populations, including novel cell populations with unexpected expression patterns.