Immune Responses against Disseminated Tumor Cells

Most cancer-related deaths are a consequence of metastases, a series of linear events, notably the invasion-metastasis cascade. The current understanding of cancer immune surveillance derives from studies in primary tumors, but disseminated cancer cells acquire mutations and, in some cases, appear to progress independently after spreading from primary sites. An early step in this process is micrometastatic dissemination. As such, the equilibrium between the immune system and disseminated cancer cells controls the fate of the cancer. Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients, but the efficacy of ICIs depends on both the tumor and its microenvironment. Data often suggest that disseminated cancer cells are not adequately targeted by the immune system. In this review, we summarize the main basic findings of immune responses against disseminated tumor cells and their organ-specific characteristics. Such studies may provide new directions for cancer immune therapy.