INTERLEUKIN-2 EXPANDED TUMOR-INFILTRATING LYMPHOCYTES AND THEIR RESPONSE TO PREOPERATIVE ALPHA-INTERFERON IN PATIENTS WITH RENAL-CELL CARCINOMA

To determine whether interferon-alpha augment antitumorigenic effect of the tumor-infiltrating lymphocytes expanded with interleukin-2, we evaluated the properties of interleukin-2 expanded tumor-infiltrating lymphocytes in 24 patients with renal cell carcinoma with or without treatment with interferon-alpha. Tumor-infiltrating lymphocytes containing tumor cells were separated from nephrectomy specimens by enzymatic digestion and Percoll gradient centrifugation, and were cultured in the serum-free medium containing interleukin-2. The number of lymphocytes increased by 10 to 1,000-fold by day 28 of culture. There was no difference in the proliferation of tumor-infiltrating lymphocytes between interferon-alpha treated patients and controls. On day 14 tumor-infiltrating lymphocytes in the treated patients contained significantly more activated cells (HLA-DR(+)) and suppressor T cells (CD8(+)11(+)) than those in the controls. No significant difference was noted, however, in the cytotoxicity of tumor-infiltrating lymphocytes against autologous and allogenic renal cell carcinoma, K-562 or Daudi cells between the experimental and control groups on day 14 or 28. No specific effects on the major histocompatibility antigens, such as modulation of the expression attributable to the preoperative treatment with interferon-alpha, were observed on renal cell carcinoma tissue when determined by immunohistochemical staining. These findings suggest that interferon-alpha does not consistently produce a beneficial effect on interleukin-2 expanded tumor-infiltrating lymphocytes in patients with renal cell carcinoma.