Pretreatment with interferon-alpha2a modulates perioperative immunodysfunction in patients with renal cell carcinoma.
BACKGROUND
Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing surgery. Here, we report on the effect of preoperative treatment with interferon-alpha2a (IFN-alpha2a).


METHODS
30 patients with a renal tumour received preoperative IFN-alpha2a 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-alpha2a 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-alpha2a. 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- alpha2a. IFN-alpha2a decreased the level of VEGF and CD4+CD25+ regulatory T-cells implicating a potential combination with tyrosine kinase inhibitors and vaccines.
Klatte
Tobias
T
Department of Urology, Otto-von-Guericke University, Magdeburg, Germany.
Ittenson
Annelore
A
Röhl
Friedrich-Wilhelm
FW
Ecke
Martin
M
Allhoff
Ernst Peter
EP
Böhm
Malte
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D015704:CD4 Antigens / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy* / Q000276:immunology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use* / Q000633:toxicity; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011183:Postoperative Complications / Q000276:immunology; D011994:Recombinant Proteins; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000970:Antineoplastic Agents; D015704:CD4 Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D053645:Interleukin-2 Receptor alpha Subunit; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A