Possible damage to immune-privileged sites in natural killer cell therapy in cancer patients: side effects of natural killer cell therapy.

Natural killer (NK) cells target the cells losing MHC-I in cancer, a phenotype that is similar to certain cells in immune-privileged sites whose milieus are separated from peripheral blood. NK cells are reported to be quantitatively and qualitatively different in immune-privileged sites from those cytotoxic ones in the blood. We hypothesize that cytotoxic and expanded NK cells induced in cancer patients may be turned into pathogenic factors if they enter immune-privileged microenvironments in susceptible individuals, such as, patients with brain cancer or a blood-brain barrier dysfunction. Therefore, in susceptible individuals, different levels of caution should be taken based on the seriousness of the side effect as discussed in this perspective.