Clonal Evolution in the Tumor Microenvironment

Cancer immunotherapy has shown efficacy in many types of cancer. However, there are many challenges, such as the difficulty in predicting therapeutic efficacy. In the tumor microenvironment, tumor cells evolve to escape the anti-tumor immune response and have capacity of proliferation, whereas immune cells also evolve along with tumor cells. Elucidating the detailed clonal evolution is helpful for the development of biomarkers for prediction of therapeutic effects and novel therapies. To elucidate clonal evolution in the tumor microenvironment, analyses at the single-cell level, rather than in bulks, is necessary for heterogeneous and highly diverse cell populations. Recently, single-cell sequencing can be used to analyze comprehensive gene expression, or it is possible to focus on specific regions, such as T-cell or B-cell receptor sequences. In addition, technologies have been developed that allow spatial analyses by a single-cell level while preserving tissue location information. Recently, new findings have been clarified using pre- and post-treatment samples from same patients to analyze the clonal progression of the tumor cells themselves and immune cells based on sequential changes in the tumor microenvironment.