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

Abstract

Introduction: Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing surgery. Here, we report on the effect of preoperative treatment with interferon-α2a (IFN-α2a). Materials and Methods: 30 patients with a renal tumour received preoperative IFN-α2a for 6 days beginning 1 week before nephrectomy, 30 did not. Parameters of cellular and humoral immunity were measured in venous blood at various intervals using flow cytometry and ELISA. Endpoints included effects on immune parameters, toxicity, and survival. Results: Toxicity was grade 1 in 52%, 2 in 30%, and 3 in 4%. During IFN-α2a administration, leukocytes, monocytes, granulocytes, B-cell marker CD19, activation markers, CD4+CD25+ regulatory T-cells, and vascular endothelial growth factor (VEGF) dropped significantly, but no difference was observed in T-cell and natural killer (NK)-cell markers, and IL-10. Postoperatively, T-cell and activation markers decreased in both groups, but CD4, CD28, IL-6, IL-10, and HLA-DR alterations were significantly less accentuated in patients who had been treated with IFN-α2a. After a median follow-up of 23 months, survival did not differ between the groups (p = 0.54). Conclusions: Perioperative immunodysfunction can be modulated by preoperative administration of IFN- α2a. IFN-α2a decreased the level of VEGF and CD4+CD25+ regulatory T-cells implicating a potential combination with tyrosine kinase inhibitors and vaccines.

Research in practice: The impact of interferon‐α therapy on immune tolerance

“…The results of these experiments are in accordance with other studies showing that treatment with IFN-α in patients with malignant melanoma or renal cell carcinoma lead to a reduction of the number and function of Tregs, whereas reduced levels of IFN-α in tumor patients seem to provoke a reduction of Tregs worsening the patients prognosis and outcome [17][18][19]. On the other hand, several studies prove that the risk of autoimmunity increases following treatment with IFN-α.…”

Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells

“…Thus, abrogation of Treg activity by IFN-a adds a novel and conceivable explanation for the immune-promoting effect of IFN-a in malignancies (3)(4)(5), including frequently observed autoimmune symptoms upon continuous therapeutic application (6,7). In line with this assertion, IFN-a treatment has been previously observed to reduce Treg numbers in patients with melanoma or renal cell carcinoma (37,38), whereas, conversely, declining IFN-a levels and impaired IFN-a signaling in patients with cancer seem to be correlated with an increase in the number of Treg and a higher risk of cancer progression (39)(40)(41). Recent reports on improved immune responses upon co-administration of IFN-a with peptide vaccines in renal (42), pancreatic (43), and colorectal cancer (44) represent additional evidence.…”

Immunotherapy during the Immediate Perioperative Period: A Promising Approach against Metastatic Disease

“…For example, a combined treatment of IFNα and continuous arterial infusion of 5FU chemotherapy 2–3 weeks postoperatively increased the 1-year overall survival (OS) of hepatocellular carcinoma patients from 30% in patients who underwent surgery alone to 100% in patients who received the combined treatment [ 82 ]. Additionally, IFNα administration during the IPP reduced the postoperative suppression of NK cell cytotoxicity [ 83 ] and decreased the circulating levels of VEGF and the number of regulatory T cells, all of which are related to a better prognosis [ 84 ]. However, a single dose of IFNα administered immediately following the transurethral resection of superficial bladder cancer did not improve OS compared to surgery alone [ 85 ].…”