The promise of precision medicine—health care and treatment decisions tailored to an individual—is on the horizon. The rapidly advancing field of immuno-oncology is leading the way, with researchers investigating how a cancer patient’s own immune system can be leveraged to treat the cancer.
As the immune cells responsible for recognizing tumor-specific antigens, T cells are capable of initiating and regulating an immune response to attack the cancer. Recent immunotherapies have focused on boosting this ability.
Identifying biomarkers that will predict whether a tumor will be sensitive to immunotherapy is a primary goal of immuno-oncology research. Tumor material is often difficult (and at times, impossible) to obtain, limited in quantity, and poor in quality, so there is a pressing need to identify biomarkers that can be obtained noninvasively. Because T cells attack cancer cells, researchers are investigating ways to use them as biomarkers. And since both T cells and cancer cells are present in blood, they can be obtained noninvasively, via liquid biopsy.
One possible way T cells could be used as biomarkers is through detection of a process called TCR convergence, via next-generation sequencing analysis. TCR stands for “T cell receptor”—the protein on the surface of a T cell that recognizes an antigen. To understand TCR convergence, you first need to know that the TCR protein can arise from multiple nucleic acid sequences. So, each T cell in a population will have its own TCR gene sequence. When individual T cells are activated due to chronic antigen stimulation and begin dividing in a process called expansion, the result is an army of T cells that recognize the same antigen but have TCRs with different sequences (convergent TCRs). The frequency of convergent TCRs may correlate with an immune response and shows promise as a potential biomarker to help guide decisions about whether to use immunotherapy as a course of treatment.
The potential of TCR convergence as a predictive biomarker may have been overlooked previously, since highly sensitive sequencing technologies are required to accurately sequence the TCR gene in a population of T cells.
In a recent paper, Looney et al. (2020) evaluated the use of TCR sequencing and convergence as a potential biomarker for immunotherapy. Using Ion Torrent sequencing technology with the Oncomine TCR Beta-LR Assay, they found that the low substitution error rate allowed them to assess TCR convergence, and helped them determine a correlation with response to immunotherapy within their sample cohort. The authors concluded that TCR convergence may be masked in other sequencing technologies, and thus the choice of sequencing platform is paramount.
While there is more work to be done to evaluate the usefulness of TCR convergence as a predictive biomarker in immuno-oncology, it is clear that choosing a highly sensitive next-generation sequencing solution will be key for cancer researchers looking to develop new immunotherapies.
To learn more, go to thermofisher.com/immune-repertoire.
Read the paper: Looney T, Topacio-Hall D, Lowman G et al. (2020) TCR convergence in individuals treated with immune checkpoint inhibition for cancer. Front Immunol https://doi.org/10.3389/fimmu.2019.02985