Interleukin-2 Expanded Tumor-Infiltrating Lymphocytes and their Response to Preoperative α -Interferon in Patients with Renal Cell Carcinoma

Abstract

To determine whether interferon-alpha could 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.

Pretreatment with Interferon-a2a Modulates Perioperative Immunodysfunction in Patients with Renal Cell Carcinoma

“…IFN-α2a decreased levels of VEGF and CD4+CD25+ Treg implicating a potential combination with tyrosine kinase inhibitors and vaccines. medium [20]. On day 14 and 18 of culture, tumour-infiltrating lymphocytes in the IFN group had a higher expression of HLA-DR, CD3, CD4, CD8, CD16, and CD57.…”

“…Recombinant human IFN-α2a (Roferon-A, Hoffmann-La Roche, Grenzach-Wyhlen, Germany) was administered subcutaneously starting a week before the operation (9 million units (MU) twice daily for 2 days), followed by a daily maintenance dose of 3 MU until 1 day before the operation. Dosage, timing, and duration of administration were selected from previous reports on perioperative immunomodulation with IFN-α2a [20,21] and treatment regimens for metastatic RCC [16]. IFN-α2a-related toxicity was assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0 (CTCAE).…”

Multi‐modal treatment of primarily using continuous subcutaneous interferon‐α injection in combination with surgery and/or radiotherapy

“…In the past, IFN was administered intramuscularly as documented in the previously published literature 9–16 . It has been reported that blood levels of IFN dropped below detectable levels at 24 h after intramuscular injection of IFN 17 .…”

“…In the past, IFN was administered intramuscularly as documented in the previously published literature. [9][10][11][12][13][14][15][16] It has been reported that blood levels of IFN dropped below detectable levels at 24 h after intramuscular injection of IFN. 17 On the other hand, blood levels of IFN were kept within a detectable range for at least 6-8 days once blood levels of IFN were kept constant following continuous subcutaneous injection of IFN.…”

Perioperative Immunmodulation beim Nierenzellkarzinom - eine Standortbestimmung

“…IE/d i.m. Interferon-á behandelt [43]. Die Eigenschaften der tumorinfiltrierenden Lymphozyten wurden dann im Nephrektomiepräparat untersucht.…”