HETEROGENEITY OF NATURAL-KILLER LYMPHOCYTE ABNORMALITIES IN COLON CANCER-PATIENTS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 95  (1) , 63-70
Abstract
The 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% vs. 16.5%, P < 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 .apprx. 2/3 of normal individuals but only 1/3 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 vs. 1046 lytic units, P = 0.04). The HNK-1- fraction (predominantly T lymphocytes) had increased NK cell functional activity in the colon cancer patients compared to normals (373 vs. 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 10 times more NK cell functional activity than did the less mature cell fraction (i.e., HNK+Leu-4+M1-) cells in normal individuals (2230 vs. 286 lytic U/107 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 [prostaglandin E2] did not appear to influence NK cell function, since NK cell function was unchanged in vitro in the presence of a prostaglandin synthesis inhibitor [Piroxicam]. Compared to normal individuals, colon cencer patients had a profound depression in the numbers of HNK-1 granular lymphocytes with a concominant decrease in their NK cell functional capability (on a per cell basis), a shift in the subsets of HNK+ cells with a significant decrease in the more functionally efficient (i.e., mature) HNK+ cells and no regulatory influence by prostaglandin-producing suppressor monocytes on NK cell function. This monoclonal HNK-1 antibody thus identified a heterogeneity of NK cell abnormalities and provided some insights into abnormal host defenses in colon cancer patients.