Tumour necrosis factor-alpha enhances the cytolytic and cytostatic capacity of interleukin-2 activated killer cells

Abstract

The cytotoxic and cytostatic responses of peripheral blood lymphocytes from eight cancer patients and splenocytes from four patients activated with rIL2 and a combination of rIL2 and rTNF-alpha were tested against two tumour cell lines. The cytotoxic response of rIL2-activated lymphocytes did not exceed the natural killer cytotoxicity values in all patients tested. In fact the killing capacity of some PBL deteriorated after rIL2 activation. The combined use of rIL2 and rTNF-alpha reversed this detrimental effect and enhanced the cytotoxic capacity of all PBL tested. In instances where high levels of killing were already achieved by rIL2 alone additional rTNF-alpha did not induce a significant change. This indicates that the role of rTNF-alpha may be to promote the response to rIL2 of PBL which react suboptimally to this lymphokine. rTNF-alpha did not only enhance cytotoxic capacity but also conferred cytostatic capacity to rIL2-activated LAK cells which were cytotoxic but unable to inhibit the growth of the surviving target cells. Natural killer cell selected K562 target cells which were less susceptible to killing by untreated lymphocytes than the parent K562 tumour cell line were killed more aggressively by rIL2 + rTNF-alpha LAK cells than by rIL2-LAK cells. No phenotypic differences were detected in these two cultures of LAK cells which indicates that the increased cytotoxic and cytostatic capacity of rIL2 + rTNF-alpha-LAK cells may be due to a higher state of activation of these cells or due to their capacity to recognise a broader spectrum of targets than rIL2-LAK cells.