Immune Responses against Disseminated Tumor Cells

SIMPLE SUMMARY: Metastasis in general represents the progression phenotype whereby cancer cells break from a malignant primary location and travel to and invade other distant organs. Theoretically, tumor cells that exit the primary tumor might be eliminated by immune cells. The immune system has the ability to recognize and eliminate malignant tumor cells; however, failed immune surveillance contributes to cancer development. Disseminated tumor cells persist and reemerge as a clinically symptomatic disease. How do disseminated tumor cells evade immune surveillance? In this context, tumor/immune system interactions play a key role and are the subject of intense scrutiny. After colonization, the immunosuppressive tumor microenvironments of metastatic lesions promote tumor growth and worsen prognosis. Here, we discuss scientific advances relating to the interaction between disseminated tumor cells and the immune cells in tissue-specific tumor microenvironments. ABSTRACT: 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.