Comprehensive serum cytokine analysis identifies IL-1RA and soluble IL-2Rα as predictors of event-free survival in T-cell lymphoma.
BACKGROUND
T-cell malignancies are heterogeneous in their clinical presentation and pathology, and have a poor prognosis. New biomarkers are needed to predict prognosis and to provide insights into signal pathways used by these cells. The goal of this study was to evaluate pretreatment serum cytokines in patients with newly diagnosed T-cell neoplasms and correlate with clinical outcome.


METHODS
We evaluated 30 cytokines in pretreatment serum from 68 untreated patients and 14 normal controls. Significantly elevated cytokines were correlated with patterns of abnormalities, event-free survival (EFS) and overall survival (OS).


RESULTS
Our data demonstrated significantly elevated levels (versus controls) of seven cytokines-epidermal growth factor (EGF), IL-6, IL-12, interferon gamma-induced protein (IP)-10, soluble interleukin (sIL)-2Rα, monokine induced by gamma interferon (MIG), and IL-1RA-in all T-cell neoplasms (P < 0.05). In the angioimmunoblastic subset, all seven cytokines except IP-10 and in the peripheral T-cell lymphoma (TCL)-not otherwise specified subset, only IP-10, sIL-2Rα, MIG, and IL-8 were statistically elevated compared with control. Of these, elevated cytokines all but EGF were predictive of an inferior EFS; IL-1RA, sIL-2Rα, and MIG predicted an inferior OS. In a multivariate analysis, sIL-2Rα [hazard ratio (HR) = 3.95; 95% confidence interval (CI) 1.61-8.38] and IL-1RA (HR = 3.28; 95% CI 1.47-7.29) levels remained independent predictors of inferior EFS. TCL cell lines secreted high levels of sIL-2Rα and expressed the IL-2Rα surface receptor.


CONCLUSIONS
This report describes the cytokines relevant to prognosis in patients with untreated TCL and provides the rationale to include serum IL-1RA and sIL-2Rα as biomarkers in future trials. Inhibition of these cytokines may also be of therapeutic benefit.
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester gupta.mamta@mayo.edu.
M
M
Gupta
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester.
M
M
Stenson
Department of Health Sciences Research, Mayo Clinic, Rochester, USA.
M
M
O'Byrne
Department of Health Sciences Research, Mayo Clinic, Rochester, USA.
M J
MJ
Maurer
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester.
T
T
Habermann
Department of Health Sciences Research, Mayo Clinic, Rochester, USA.
J R
JR
Cerhan
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA.
G W
GW
Weiner
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester.
T E
TE
Witzig
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016399:Lymphoma, T-Cell / Q000097:blood* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D055815:Young Adult
D014408:Biomarkers, Tumor; D053590:Interleukin 1 Receptor Antagonist Protein; D053645:Interleukin-2 Receptor alpha Subunit
AITL; IL-1RA; PTCL-NOS; T-cell lymphoma; cytokines; sIL-2Rα