Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population

Background One of the most critical questions in immunosurveillance is whet her differences between individuals with regards to natural immunological h ost defence can predict future development of cancer. Although this questio n has so far remained open, there are clear indications of significant role s of several naturally cytotoxic lymphocytes in preventing the development of cancer. We began a prospective cohort study among a Japanese general pop ulation in 1986, using various immunological and biochemical markers. Methods Natural cytotoxic activity of peripheral-blood mononuclear cells wa s assessed by isotope-release assay in 3625 residents of a Japanese populat ion mostly older than 40 years of age, between 1986 and 1990. Immunological and biochemical markers were also measured, and participants were given a questionnaire on lifestyle. We did an Ii-year follow-up survey of the cohor t members looking at cancer incidence and death from all causes, and analys ed the association between cytotoxic activity of peripheral-blood lymphocyt es assessed at baseline and cancer incidence found in the subsequent follow -up. Findings 154 cancer cases were used in the analysis. When we categorised th e cytotoxic activity of peripheral-blood lymphocytes by tertiles, age-adjus ted relative risk of cancer incidence (all sites) was 0.72 (95% CI 0.45-1.1 6) for men with high cytotoxic activity, and 0.62 (0.38-1.03) for men with medium cytotoxic activity, taking the risk of those with low cytotoxic acti vity as reference. For women with high cytotoxic activity relative risk was 0.52 (0.28-0.95), and for those with medium cytotoxic activity 0.56 (0.31- 1.01). For both sexes with high and medium cytotoxic activity risk was 0.63 (0.43-0.92) and 0.59 (0.40-0.87), respectively. Interpretation Our results indicate that medium and high cytotoxic activity of peripheral-blood lymphocytes is associated with reduced cancer risk, wh ereas low activity is associated with increased cancer risk suggesting a ro le for natural immunological host defence mechanisms against cancer.