The role of natural killer (NK) cells in the control of tumor metastasis

Abstract

Elucidation of the host defense mechanisms that control tumor dissemination is essential for the design of successful approaches for the prevention and therapy of tumor metastasis. It has been demonstrated that immunity against tumor-specific antigens [1, 2] and generalized nonspecific stimulation of the immune response [3, 4] may inhibit metastasis formation. In contrast, immunosuppression enhances metastatic spread of immunogenic tumors [5, 6]. Host responses mediated by T lym-phocytes [6], macrophages [7, 8] and NK cells [9] participate in host resistance against tumor metastasis. Considering the nature of the metastatic process [10–12], such effector mechanisms could prove effective in controlling lymphatic and hematogenous spread of tumor cells, although they might exert only a limited effect against the primary tumor. For example, once tumor cells enter the circulation, in the form of single cells or small clumps [13], they are confronted with highly destructive immune and nonimmune host defense mechanisms that might not exist within the primary tumor mass. Indeed, the majority of tumor cells that enter the circulation are destroyed and only a small fraction survive and develop into secondary tumor foci in the organ parenchyma [14]. Little is known about the mechanisms responsible for the rapid destruction of most circulating tumor cells. In this chapter, the in vivo role of NK cells in the destruction of circulating tumor cells and the inhibition of hematogenous tumor metastasis will be discussed.