Researchers at the University of Texas MD Anderson Cancer Center have discovered a new blood-based biomarker that helps identify and characterize asymptomatic Lynch syndrome (LS) patients who are more likely to develop cancer based on early immune detection signatures. This allows clinicians to stratify patients based on their individual risk level.
This study nature communicationsled by Eduardo Villar Sánchez, MD, Interim Chair of Clinical Cancer Prevention. These results advance our understanding of T cell responses in LS carriers and provide personalized insights for early cancer detection, monitoring, and therapeutic intervention in these populations.
Providing a potential non-invasive blood test to track cancer risk and immune activation in Lynch syndrome patients would be a major step forward for this patient population. These are valuable insights into the immune response and can help personalize how to monitor and direct preventive strategies. ”
Eduardo Villar Sánchez, MD, Interim Chair of Clinical Cancer Prevention
What is Lynch syndrome? Why did researchers examine blood samples?
Lynch syndrome is a genetic disease associated with germline mutations in DNA mismatch repair genes. LS patients have a genetic predisposition to developing cancers with microsatellite instability, particularly colorectal and endometrial cancers, and often develop cancer at a younger age than the general population. A way to understand an individual’s level of risk for developing cancer could help clinicians provide appropriate monitoring and intervention to improve outcomes.
These microsatellite mutations result in insertions or deletions of DNA sequences and also generate tumor-specific neoantigens. These neoantigens are protein fragments on cancer cells that T cells recognize as foreign and trigger an immune response. Researchers have sequenced the T cell receptor (TCR), which helps T cells identify and attack threatening neoantigens on cancer cells.
They characterized TCRs found in peripheral blood mononuclear cell (PBMC) samples from 277 people, which contain important T cells involved in immune defense. These included 102 LS survivors, 130 carriers (previous survivors) with no history of cancer, and 45 controls without LS or cancer. They also performed TCR sequencing on three cancerous and 11 precancerous colorectal tissues that matched these PBMC samples.
What did the blood and tissue samples show?
In colon tumors and pre-cancerous tissues, specific T cells (identified by their corresponding TCRs) proliferated in response to these tumor-specific neoantigens. Up to 41% of expanded TCRs from colon precancers and tumors were detected in LS carriers but not in people without LS, suggesting that the immune system is monitoring and responding to early signs of cancer.
The researchers then used this data to generate a classification model that differentiates between LS carriers and control samples simply by looking at TCR patterns in the blood. This model helped identify LS carriers along with cancer-free pre-LS survivors, independent of cancer history.
What does this research mean?
This study found that circulating cancer-associated TCRs can be identified in blood samples of LS carriers, providing a unique immune signature that can detect individuals at high risk of developing cancer. Although further validation is required, this blood-based biomarker could serve as a non-invasive tool for early detection, risk assessment, and personalized monitoring of LS patients.
sauce:
University of Texas MD Anderson Cancer Center
Reference magazines:
Deng, N. others. (2026). Genomic analysis of T-cell receptors reveals unique immune signatures of Lynch syndrome. nature communications. DOI: 10.1038/s41467-026-71243-z. https://www.nature.com/articles/s41467-026-71243-z
