Abstract

Despite the well-demonstrated involvement of both interleukin 2 (IL-2) and interleukin 12 (IL-12) in the activation of host anti-cancer response, the knowledge of IL-2-IL-12 interactions has still to be better investigated. This study was performed to evaluate the effects of subcutaneous (s.c.) low-dose IL-2 on IL-12 secretion in metastatic cancer patients. The study included 19 evaluable metastatic renal cell cancer patients, who received s.c. low-dose IL-2 (6 MIU day(-1) for 6 days per week for 4 weeks) as a first-line immunotherapy of their metastatic disease. Serum levels of IL-12 were measured using an enzyme immunoassay on venous blood samples collected before the immunotherapy and at 1-week intervals. The clinical response consisted of partial response (PR) in four and stable disease (SD) in eight patients, whereas the other seven patients progressed. Mean serum levels of IL-12 observed in the overall patients significantly increased in response to IL-2 injection. Moreover, by evaluating IL-12 variations in relation to the clinical response, a marked significant increase in IL-12 mean values occurred in patients with response or SD, whereas the progressing patients showed a significant decline in IL-12 levels during IL-2 administration. Finally, IL-12 mean pretreatment values observed in patients who progressed were significantly higher than those seen in non-progressing patients. This study shows that low-dose IL-2 immunotherapy of cancer may stimulate the in vivo release of IL-12, and it would suggest that IL-2-induced IL-12 enhancement is associated with a favourable prognosis.

Highlights

  • Evaluable patients were 19 out of 20, with the last patient rapidly progressing before concluding the first cycle of treatment

  • IL- 12 secretion in response to interleukin 2 (IL-2) injection would not represent a biological epiphenomenon, but it could play a role in influencing the clinical response to IL-2 cancer immunotherapy

  • On the basis of its anti-cancer activity (Banks et al, 1995) and on its more frequent increase in nonprogressing patients, it is possible to hypothesize that the antitumour efficacy of low-dose IL-2 regimen may be mediated at least in part by an increased endogenous production of IL- 12, which has been seen to synergize with IL-2 in inducing objective tumour regressions in experimental conditions (Wigginton et al, 1996)

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Summary

Introduction

By evaluating IL- 12 profile in relation to the clinical response, IL- 12 mean concentrations showed a highly significant increase in response to IL-2 only in patients with response or SD, whereas its levels significantly decreased in patients who had a PD.

Results
Conclusion
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