Immuno-oncology and check point inhibitors are a part of the exploding field of modulating the body’s own immune response to fight cancer. When checkpoint inhibitors work, they can be very effective. However, they don’t always work and figuring out why that is the case is critical to discovering the next iteration of immune system targeting therapeutics.
Broadly and briefly, the problem arises when T-cells are either in the tumor but suppressed by the tumor microenvironment, or the T-cells are physically not present. Each case results in T-cells that are either too suppressed to be activated by the treatment, or T-cells that are active in the periphery of the tumor unable to have a useful effect. In either case, the patient’s response to a check point inhibitor will likely be poor and the tumor can be classified as a cold tumor. The tumors mutational burden will also influence the results of treatment, but for the purposes of this discussion lets focus on the T-cell.
These cold tumors have a very hostile tumor microenvironment which can suppress and stymie the immune response resulting in unchecked growth. The stroma physically blocks T-cell infiltration. There is selective secretion of pro Regulatory T-cell cytokines to recruit the suppressive cells. And if the T-cells can infiltrate, there are anti-proliferation and pro-apoptotic factors waiting.
Studying how T-cells invade and what changes can be made to the tumor microenvironment to affect the amount and rate of invasion is a critical research question. At Visikol, we commonly work with complex 3D cell culture systems to mimic this in vivo process and have found that they are able to provide assay endpoints that are just not possible with traditional 2D cell culture assays. Using these 3D cell culture models combined with high content imaging, we are able to track T-cells as they invade into 3D cell culture models and corelate the location of T-cells with the death of a particular cell subtype. If you have questions about how to study T-cells and how they invade into tumors, please reach out to one of our scientists.