Natural killer cell activity in tumor-draining lymph nodes: investigations in patients with malignant melanoma and head and neck cancer

Abstract

Mononuclear cells isolated from peripheral blood (PB) of patients with malignant melanoma and head and neck cancer were tested for natural killer (NK) cell activity against K562 targets. Significantly lower levels of NK activity were observed in patients with malignant melanoma with metastatic disease in comparison to stage I and control population. In head and neck cancer NK activity was normal in tumor stage 1-2 and significantly impaired in stage 3-4. Mononuclear cells (MNC) isolated from primary tumor-draining lymph nodes (LNs) had significant NK activity in 12 of 25 (48%) of melanoma and 9 of 19 (47%) of head and neck lymph nodes at E:T 40:1. Reactivity was always significantly lower than in autochthonous Preincubation (+37 degrees C, 18 h) of lymph node mononuclear cells (LNMNC) resulted in a significant increase in cytotoxicity in 36% of melanoma and 32% of head and neck LNs. Simultaneous incubation with interferon (IFN)-alpha resulted in 24% of melanoma and 44% of head and neck LNs in a significant further augmentation of NK activity. LNMNC were furthermore found to react in 2-24% (mean 7.79 +/- 2.1) with the monoclonal antibody HNK-1, which identifies a certain proportion of NK cells. No correlation was found between percentage HNK-1+ cells and the expression of NK activity. From these studies it may be concluded that tumor draining LNs contain cells which are active against K562 targets expressing low but variable levels of cytotoxicity. NK cell activity can be increased by incubation of LNMNC at 37 degrees C with or without addition of IFN. These results suggest that modulation of NK activity in tumor draining LNs might be achieved by local application of biological response modifiers, which might finally lead to an increase of local tumor defense mechanisms.