TRANSCRIPTION FACTOR ACTIVATION IN LYMPHOKINE-ACTIVATED KILLER-CELLS AND LYMPHOCYTES FROM PATIENTS RECEIVING IL-2 IMMUNOTHERAPY

Administration of the cytokine interleukin-2 (IL-2) can result in ther apeutic benefits for individuals with renal cell carcinoma and melanom a. Here we report an analysis of the transcription factor families AP- 1, Spl, NF-KB, and signal transducers and activators of transcription (STAT) in cancer patients' lymphocytes before and after IL-2 immunothe rapy, as assessed by a gel-shift assay. An in vitro surrogate of IL-2 immunotherapy is the incubation of fresh peripheral blood mononuclear cells (PBMC) from healthy individuals in IL-2 for several days, result ing in the production of lymphokine-activated killer (LAK) activity in these cultures. One purpose of this study was to describe the profile of transcription factor activation in these different populations, an d assess whether the patterns observed correlated with functional diff erences in these cells. Prior to in vivo IL-2 administration, the typi cal binding pattern of transcription factors in PBMC from patients res embled that seen in fresh PBMC from healthy individuals. Over a 3-week course of IL-2 therapy, in most patients the binding patterns of AP-1 , Spl, and NF-kappa B proteins changed to resemble those seen in PBMC activated by IL-2 in vitro. However, the cells obtained from IL-2-trea ted patients did not have low-level constitutive expression of STAT bi nding factors as did LAK cells. When these patient cells were further stimulated by IL-2 in vitro, additional differences in STAT induction patterns were noted. These data provide further information on the mol ecular events occurring in immune cells generated through in vivo and in vitro administration of IL-2, and further document that there is no t a precise congruence between PBMC activated in vivo and in vitro by IL-2.