The diversity of T and B cells in terms of their receptors is huge in the invertebrate’s immune system, to provide broad protection against the vast diversity of pathogens. Immune repertoire is defined as the sum of total subtypes that makes the organism’s immune system, either T cell receptor or immunoglobulin. Before the emergence of high-throughput sequencing, the study on immune repertoire is limited by methodology, as it is impossible to capture the whole picture by the low-throughput tools. The massive paralleled sequencing suits perfectly the study on immune repertoire. In this thesis, I describe the experimental and analytical methodologies we developed for immune repertoire analysis. We have devoted extensive efforts on the optimization and evaluation of these pipelines. We then use the tools to investigate the characteristics and dynamic of immune repertoire on both blood and solid cancer. Specifically, we provide analysis on leukemic IGH sequences and their evolution in B-cell acute lymphoblastic leukemia, and monitor the dynamics of IGH repertoire during chemotherapy. Further, the TCR repertoire of infiltrated T lymphocytes in breast tumor and adjacent tissues was analyzed. We describe numerous interesting findings that might provide hints on immunotherapy of breast cancer.