Reduced T cell repertoire diversity in the peripheral blood of diagnosed cancer patients

One measure of an individual’s immune repertoire is the diversity of antigen response present in their immune cells, which can be estimated through the sequences of T-cell receptors in the blood. We developed a semi-quantitative multiplex PCR method to amplify the complementarity-determining region 3 (CDR3) sequences of T cell receptors (TcRs) determined by the 454 sequencing platform. Three subsets of T cells (cytotoxic [Tc], helper [Th], and regulatory [Tr]) from peripheral blood samples of normal control, lung cancer, colon cancer, and breast cancer patients were analyzed in this study. Specific CDR3s were found to be unique to two of the three particular types of cancer tested, and other CDR3s to be specific to normal controls. For potential application to clinical settings, we developed the D50 test to quantitatively measure the level of repertoire diversity in a sample. We found that D50 values were significantly lower in cancer samples in all three subsets of T cells compared to normal controls, while D50 values of Tr cells were better able to distinguish normal from cancer samples than those of either Tc or Th cells. Previous studies have shown that loss of immune repertoire diversity is associated with various diseases, and we suggest that the D50 test could be used as a screening test to evaluate health status. In addition, the expression profile of disease-specific CDR3s may be used as biomarkers for early diagnosis, prognosis, or disease management.