Upregulation of interleukin-12 receptor on peripheral blood mononuclear cells and HLA class I, HLA class II or ICAM-1 on melanoma cells by B7.1 and interleukin-12: a mechanism for immunostimulatory impact of melanoma cells adenovirally transfected with B7.1 and IL12?

Melanoma is an immunogenic tumour and may express both HLA class 1 and clas s II molecules. These can be recognized by cytotoxic T-cells. Melanoma cell s can evade immunosurveillance due to the lack of co-stimulatory molecules such as B7.1 or B7.2. Interleukin-12 (IL12) exerts antitumour effects, and B7.1 and IL12 synergistically induce effective antitumour immunity. We inve stigated the immunostimulatory potential of melanoma cells adenovirally tra nsduced with B7.1, IL12 or B7.1 plus IL12. We observed that: (i) melanoma c ells transduced with B7.1 plus IL-12 can elicit a strong proliferative resp onse from peripheral blood mononuclear cells (PBMCs); (ii) a high level of TH1 cytokine production from PBMCs was induced by melanoma cells transduced with Adv-B7.1 plus Adv-IL12; (iii) the expression of HLA class I antigens, HLA class II antigens or ICAM-1 antigens was higher on melanoma cells tran sduced with Adv-IL12 or Adv-B7.1 plus IL12 than those transduced with Adv-L acZ or wild-type melanoma cells; and (iv) the expression of IL12 receptors on PBMCs was upregulated by melanoma cells transfected with Adv-IL12 or Adv -B7.1 plus IL12. Thus, melanoma cells transduced with both Adv-IL12 and B7. 1 may represent another clinical approach for antimelanoma gene therapy. (C ) 2000 Lippincott Williams & Wilkins.