Heterogeneity of natural killer lymphocyte abnormalities in colon cancer patients.
p6e monoclonal antibody HNK-1 reacts exclusively with human granular lymphocytes that comprise 16 +/- 1.4% of blood mononuclear cells. In normal individuals, almost all natural killer (NK) and killer (K) cell function resides in this lymphocyte subset. The level of HNK-1+ granular lymphocytes, their stage of differentiation, and NK cell function were examined in 70 colon cancer patients and the results compared with data for 114 age-matched normal individuals. Median levels of granular lymphocytes were significantly depressed in colon cancer patients compared to controls (9% versus 16.5%, P less than 0.0001). Despite the depressed numbers of circulating HNK-1+ cells, NK cell function in the colon cancer patients was essentially the same as in normals (P = 0.78). The HNK-1+ lymphocyte level correlated exactly with NK cell function in about two thirds of normal individuals but only one third of colon cancer patients (P = 0.025). Three possible mechanisms for this dichotomy were examined. First, lymphoid cell subpopulations purified with a fluorescence-activated cell sorter (FACS) were examined for altered NK cell functional activity. HNK-1+ cells from the colon cancer patients exhibited significantly less NK functional activity compared to normals (796 versus 1046 lytic units, P = 0.04). Interestingly, the HNK-1- fraction (predominantly T lymphocytes) had increased NK cell functional activity in the colon cancer patients compared to normals (373 versus 218 lytic units, P = 0.0001). Purified monocytes did not contribute to NK cell functional activity. Second, the functional maturity of the HNK-1+ lymphocytes was correlated with NK activity. Two subsets of HNK-1+ cells were identified by surface membrane markers and purified with the FACS. The more mature HNK-1+ subset (i.e., HNK+Leu-4-M1+) exhibited almost ten times more NK cell functional activity than did the less mature cell fraction (i.e., HNK+Leu-4+M1-) cells in normal individuals (2230 versus 286 lytic units/10(7) cells). Further analysis demonstrated that the ratio of mature to immature HNK+ cells in normal individuals was 3:1, while it was decreased to a 1:1 ratio in colon cancer patients P = 0.005). Third, the influence of prostaglandin-mediated suppression on NK cell activity was examined. PGE2 did not appear to influence NK cell function, since NK cell function was unchanged in vitro in the presence of a prostaglandin synthesis inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)
D000911:Antibodies, Monoclonal / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000503:physiopathology; D015232:Dinoprostone; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D011458:Prostaglandins E / Q000494:pharmacology; D011863:Radioimmunoassay
D000911:Antibodies, Monoclonal; D011458:Prostaglandins E; D015232:Dinoprostone