Single-cell RNA and TCR sequencing reveals preferential Vδ1+ usage with expanded CDR3 identity profiles in MSS CRC γδ T cells. 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 patient treatment. The study was recently published in Nature Communications.
The researchers, led by Victoria Stary (Department of General Surgery, Comprehensive Cancer Center MedUni Vienna and University Hospital Vienna), focused their research on a particular type of immune cell, called γδ T cells, whose role in immune disorders associated with colorectal cancer has not yet been studied.
Unlike the much more 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 respond directly to signals from potentially diseased cells. This makes them a highly effective component of the immune system.
The researchers’ complex analyses show that a particular subset of these cells, the Vδ1+ T cells, do not function sufficiently to effectively fight cancer in patients with MSS CRC. The scientists identified as triggers certain connective tissue cells (fibroblasts) that release substances that block the activity of the Vδ1+ T cells.
“As we discovered, this blockage can be partially reversed if a certain molecule called TIGIT is inhibited on Vδ1+ T cells. This allows the T cells to fight cancer cells a little better again,” Stary reports.
By far the most common form of colon cancer
Microsatellite stable tumors account for 85–90% of colorectal cancers. Unlike microsatellite unstable colorectal cancer (MSI CRC), patients with MSS CRC respond only to a limited extent to immunotherapies aimed at activating the body’s immune system to fight the tumor.
The new knowledge gained provides a possible explanation for the treatment failure and suggests promising avenues. “Our study shows that not only the known αβ T cells, but also 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 the success of MSS CRC treatment,” Stary says.
More information:
Victoria Stary et al., Dysfunctional tumor-infiltrating Vδ1+ T cells in microsatellite-stable colorectal cancer, Nature Communications (2024). DOI: 10.1038/s41467-024-51025-1
Provided by the Medical University of Vienna
Quote: Colorectal cancer: New approach for better efficacy of immunotherapies (2024, August 27) retrieved on August 27, 2024 from
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