What is Tumor Mutational Burden (TMB)?
Tumor Mutational Burden (TMB) refers to the total number of mutations per megabase of DNA in a tumor. It serves as a quantitative measure of the mutational load within a cancerous tissue. TMB has gained significant attention as a potential biomarker for predicting the response to
immunotherapy, particularly immune checkpoint inhibitors.
Why is TMB Important in Cancer Treatment?
TMB is important because it has been associated with the effectiveness of certain cancer treatments. High TMB is thought to increase the number of
neoantigens, novel proteins that arise from mutations and can be recognized by the immune system. This can enhance the efficacy of immunotherapies, which rely on the immune system to identify and attack cancer cells. Thus, TMB can guide personalized treatment strategies and improve outcomes for patients.
How is TMB Measured?
TMB is measured using
next-generation sequencing (NGS) technologies that can analyze the entire exome or a panel of cancer-related genes. The number of somatic mutations is counted and normalized per megabase of sequenced DNA to calculate the TMB score. This score can vary significantly depending on the sequencing platform and the gene panel used.
What Cancers Have High TMB?
Cancers with high TMB include melanoma, lung cancer, bladder cancer, and certain types of
colorectal cancer. These cancers often have a high number of mutations due to factors such as environmental exposure or genetic predispositions, making them more likely to express neoantigens that can be targeted by the immune system.
Is TMB a Reliable Biomarker?
While TMB has shown promise as a biomarker, it is not without limitations. The reliability of TMB can be influenced by the heterogeneity of tumors, differences in sequencing methods, and the cutoff values used to define "high" TMB. Additionally, TMB alone may not fully predict response to
checkpoint inhibitors, and it is often used in combination with other biomarkers, such as PD-L1 expression, for a more comprehensive assessment.
What are the Challenges in Using TMB Clinically?
There are several challenges in incorporating TMB into clinical practice. These include standardizing TMB measurement across different platforms and establishing clinically relevant thresholds for TMB levels. Moreover, the cost and accessibility of comprehensive genomic testing can be a barrier for routine use in some healthcare settings.
What is the Future of TMB in Cancer Research?
The future of TMB in cancer research looks promising, with ongoing studies aiming to refine its predictive accuracy and integrate it with other biomarkers. Advances in
bioinformatics and sequencing technologies are expected to improve the precision of TMB assessment. Additionally, research is focused on understanding the biological mechanisms behind TMB and its role in shaping the tumor microenvironment.
Conclusion
Tumor Mutational Burden is an evolving biomarker that holds potential for guiding cancer treatment decisions, particularly in the realm of
immuno-oncology. As research progresses, it is likely that TMB will become a more integral part of personalized cancer therapies, offering hope for improved patient outcomes.
