Cancer immunotherapy with natural killer cells.

Natural killer (NK) cells were first identified for their ability to kill tumor cells of different origins. They were subsequently found to be able to kill some normal cells, especially those infected by certain viruses. Natural killer cells are a distinct lymphocytic population, with the morphology of large granular lymphocytes, and they lack surface Ig or T-cell markers. Natural killer cytotoxicity is enhanced in vitro in the presence of cytokines such as interleukin-2 and interferon-alpha. However, when used in immunotherapy, these cytokines have not consistently augmented NK activity or shown antitumor effects. One explanation for this divergence is that NK cell activity is suppressed in tumor tissues by various factors, including reactive oxygen species produced by infiltrating monocytes and macrophages. Agents that inhibit the generation of reactive oxygen species, such as histamine, may abrogate the suppression exerted on NK cells by monocytes/macrophages, therefore offering potential therapeutic benefit as immunoadjuvants. Copyright 2002, Elsevier Science (USA). All rights reserved.