The use of the checkpoint blockade has been an important advancement in the field of cancer treatments, but it seems that not all tumors will react to immunotherapy.
A team of researchers decided to explore T cell exhaustion in the case of two types of colorectal cancers: microsatellite instability (MSI), which response to PD-1 blockade and microsatellite stable(MSS) that are resistant to PD-1 focused therapies.
In both cases, T cells that can infiltrate through tumors have been exhausted, but the researchers observed that T cell exhaustion in MSS colorectal (CRCs) is powered by VEGF-A. With the help of experiments on mice, the researchers learned that a continued blockade of both PD-2 and VEGF-A blockades made MSS CRCs more susceptible to the PD-1 blockade.
The new data is quite important since it shows that in-depth characterization of checkpoint-resistant tumors can contribute to the discovery of vulnerabilities that render them sensitive to immunotherapy.
Scientists are working hard on advanced antibodies that can stimulate exhausted T cells in patients affected by cancer by interacting with the structure of immune checkpoint receptors and their ligands. Treatments that include immune checkpoint inhibitors are prescribed quite often against a large number of cancer types.
However, statistics have shown that patients who battle MSS CRCs do not seem to respond to PD-1 blockers if no other stimulants are present as the response rates tend to remain 0. This hinders the utility and applicability of checkpoint blockade therapies among a significant number of patients as alternate strategies have to be used.
During the study, the researchers observed that a coincident increase of the inhibition of vascular endothelial growth factor-A led to improvement among T cells, which were able to overcome the exhaustion.
While the current amount of data is quite impressive further research is already underway as the researchers wish to learn more about the exhaustion of T-cells. A study was published in a scientific journal