Application of High-Throughput Sequencing Approaches in Immunogenomic Research : Diversity and Clonal Selection in the Human T-Cell Repertoire for Colonrectal Cancers

Colorectal cancer (CRC) is the second most common cancer and is also the third leading cause of cancer death in Taiwan. Surgery remains the mainstay of therapy, but recurrence after surgery of CRC occurs at a constant rate according to the stage of the disease. Although chemotherapy has also been applied in the treatment of colorectal cancer, a large amount of poorer responses still exist. Therefore it is valuable to discover the significant predictive biomarkers to specifically prevent the pathogenesis of colorectal cancer. It is known that V(D)J recombination and the clonal selection of immune repertoire is constructed to specifically against to disease-related antigens. The immune repertoire can be varied/changed among individuals due to influences of microenvironment and diseases such as cancer. However, whether immune repertoire changes in colorectal tumor can predict therapeutic efficiency and prognosis is still elusive. We plan to conduct a series of experiments to address the questions. The specific aims to be tested are: (1) To identify the V(D)J sequences of T cell receptor and construct profiles of T-cell repertoire in colon cancer patients. (2) To determine the correlations between immune repertoire characteristics and clinical profiles. (3) To study the relationship between T-cell repertoires and the impact of therapeutic interventions. This project is significant and innovative because 1) immune repertoire characteristics play an important role in the variety of physiological functions and we are addressing a novel aspect of T cell receptor V(D)J recombination in colorectal cancer. This study may facilitate us to identify useful immune repertoires for the prevention as well as treatment of this disease 2) our study will allow us to identify the new functional roles of immune repertoire which has little knowledge in tumor development 3) the results may be critical to design a new target for drugs (antibody) aimed at T cell receptor and its related diseases, and finally, 4) Using a combination of genomics/bioinformatics tools (genotyping, T cell sequencing and NGS) and clinical approaches (clinical profiles, disease status, therapeutic outcomes), our study will be helpful in the treatment of colorectal cancer