Researchers at The University of Texas MD Anderson Cancer Center have discovered a new blood-based biomarker that can help identify and characterize asymptomatic people with Lynch Syndrome (LS) who are more susceptible to developing cancer based on early immune detection signatures, allowing clinicians to stratify patients based on their personal risk level.<\/p>\n
The study, published in Nature Communications, was led by Eduardo Vilar-Sanchez, M.D., Ph.D., chair ad interim of\u00a0Clinical Cancer Prevention. The results advance our understanding of T cell responses in LS carriers, providing personalized insights for early cancer detection, monitoring and therapeutic interventions for these individuals.<\/p>\n
Providing a potential non-invasive blood test to track cancer risk and immune activity in patients with Lynch Syndrome is a tremendous step forward for this patient population. These are valuable insights into immune responses that can help personalize the way we monitor and direct prevention strategies.”<\/p>\n
Eduardo Vilar-Sanchez, M.D., Ph.D., chair ad interim of\u00a0Clinical Cancer Prevention<\/p>\n
What is Lynch Syndrome and why did the researchers examine blood samples?<\/p>\n
Lynch Syndrome is a hereditary condition involving mutations in the germline of DNA mismatch repair genes. People with LS have a genetic predisposition to develop cancers with\u00a0microsatellite instability, especially colorectal and endometrial cancer,\u00a0and they often develop cancers at a younger age than the general population. Having a way to understand an individual’s level of risk for developing cancer could help clinicians offer appropriate surveillance and intervention to improve outcomes.<\/p>\n
These microsatellite mutations, which result in insertions or deletions of DNA sequences, also create tumor-specific neoantigens. These neoantigens are protein fragments on cancer cells that T cells<\/a> recognize as foreign, triggering an immune response. The researchers sequenced T cell receptors (TCR), which help T cells identify and attack threatening neoantigens on cancer cells.<\/p>\n They characterized the TCRs found in peripheral blood mononuclear call (PBMC) samples \u2013 which contain crucial T cells involved in immune defense \u2013 from 277 people, including 102 survivors of LS, 130 carriers without a history of cancer (previvors), and 45 controls without LS or cancer. They also performed TCR sequencing in the colorectal tissues of three cancers and 11 pre-cancers matched to those PBMC samples.<\/p>\n What did the blood and tissue samples show?<\/p>\n In colon tumors and pre-cancer tissues, certain T cells \u2013 identified by their corresponding TCRs \u2013 were expanded in response to these tumor-specific neoantigens. Up to 41% of the expanded TCRs from colon pre-cancers and tumors were detected in LS carriers but not in people without LS, suggesting that the immune system is surveilling and responding to early signs of cancer.<\/p>\n The researchers then used this data to generate a classification model that distinguishes LS carriers from control samples simply by looking at the TCR patterns in blood. This model helped identify LS carriers, independent of cancer history, along with cancer-free LS previvors.<\/p>\n What are the implications of this study?<\/p>\n The study found that circulating cancer-associated TCRs can be identified in blood samples from LS carriers, providing unique immune signatures that could detect individuals at higher risk of cancer development. While further validation is needed, this blood-based biomarker<\/a> could serve as a non-invasive tool for early detection, risk assessment and personalized surveillance for patients with LS.<\/p>\n Source:<\/p>\n University of Texas M. D. Anderson Cancer Center<\/a><\/p>\n Journal reference:<\/p>\n