by Medical University of Vienna

Single-cell RNA- and TCR sequencing reveal favored Vδ1+ usage with expanded CDR3 identity patterns in γδ T cells of MSS CRC. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-51025-1

The most common form of colorectal cancer, microsatellite-stable colorectal cancer (MSS CRC), can currently only be treated to a limited extent with modern immunotherapies. A research team led by MedUni Vienna has now identified the possible cause of treatment failure and thus found a way to improve treatment for patients. The study was recently published in Nature Communications.

The researchers, led by Victoria Stary (Department of General Surgery, Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna), focused their investigations on a special type of immune cell, known as γδ T cells, whose role in immune disorders associated with colorectal cancer has not yet been investigated.

In contrast to the much better-studied αβ T cells, which only recognize foreign bodies in the body when they are presented to them by other cells, γδ T cells can react directly to signals emitted by potentially diseased cells. This makes them a highly effective component of the immune system.

The researchers' complex analyses show that a certain subgroup of these cells, the so-called Vδ1+ T cells, do not function sufficiently to effectively fight the cancer in patients with MSS CRC. The scientists identified certain connective tissue cells (fibroblasts) that release substances that block the activity of the Vδ1+ T cells as the trigger for this.

"As we have discovered, this blockade can be partially reversed if a certain molecule called TIGIT is inhibited on the Vδ1+ T cells. This allows the T cells to fight the cancer cells a little better again," reports Stary.

Most common form of bowel cancer by far

At 85% to 90%, microsatellite-stable tumors make up the vast majority of colorectal cancers. In contrast to microsatellite unstable colorectal cancer (MSI CRC), patients with MSS CRC respond only to a limited extent to immunotherapies aimed at activating the body's own immune system to fight the tumor.

The newly gained insights provide a possible explanation for the therapy failure and at the same time point to promising options. "Our study shows that not only the known αβ T cells, but also the γδ T cells play a role in the most common form of colorectal cancer.

"Future research could specifically target γδ T cells and their interactions with other cells in the tumor microenvironment, such as fibroblasts, to develop ways to improve treatment success in MSS CRC," says Stary.

More information: Victoria Stary et al, Dysfunctional tumor-infiltrating Vδ1+ T lymphocytes in microsatellite-stable colorectal cancer, Nature Communications (2024). DOI: 10.1038/s41467-024-51025-1

Journal information: Nature Communications 

Provided by Medical University of Vienna