Serum Levels of Interleukin-9 Correlate with Negative Prognostic Factors in Extranodal NK/T-Cell Lymphoma

Abstract

Interleukin-9 (IL-9) is more functionally diverse than previously expected, especially with regards to lymphomagenesis. However, the relationship between IL-9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less well established. Patients with this lymphoma in Sun Yat-Sen University Cancer Center between January 2003 and March 2013 were systematically reviewed in an intention-to-treat analysis. Baseline serum IL-9 levels were determined using sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients were enrolled in this study. The mean concentration of serum IL-9 for all patients was 6.48 pg/mL (range: 1.38–51.87 pg/mL). Age, B symptoms and local lymph node involvement were found to be related to high serum IL-9 levels. Patients with low IL-9 levels tended to have higher rates of complete remission. Notably, the median progression-free survival (PFS) and overall survival (OS) were longer in the low IL-9 level group than in the high IL-9 level group (PFS: 68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently predictive of shorter OS. Serum IL-9 is closely related to several clinical features, such as age, B symptoms and local lymph node involvement. It can also be a significant independent prognostic factor for extranodal NK/T-cell lymphoma, which suggests a role for IL-9 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.

Clinical characteristics and treatment of 69 patients with extranodal natural killer T-cell lymphoma

“…This retrospective study analyzed the clinical characteristics of patients with ENKL. In agreement with previous studies (2,13), our data demonstrated that ECOG score, stage, IPI, presence of B symptoms and treatment with radiotherapy were independently associated with the survival of ENKL. However, the LDH level did not exhibit an independent association with survival, which differed from the results of other studies (1,8), despite the fact that the mOS of patients with elevated serum LDH was below average (70 vs. 96 months) (Table I).…”

“…Extranodal natural killer-T cell lymphoma (ENKL) is a subtype of non-Hodgkin lymphoma (1), occurring more frequently in Asia compared with Western countries (2). According to a recent survey, ENKL is the second most common extranodal lymphoma subtype in China after large B-cell lymphoma (3).…”

Nasal-type NK/T-cell lymphomas are more frequently T rather than NK lineage based on T-cell receptor gene, RNA, and protein studies: lineage does not predict clinical behavior

“…35 Biomarkers associated with poor prognosis included the expression of p53 and p63, and high serum levels of interleukin-9, CXCL13, serum VEGF, and survivin. [36][37][38][39] EBV-encoded latent membrane protein expression correlated with the phosphorylation of RelA and Akt possibly had a favorable impact on clinical outcome in patients with ENKTLs. 20,40 Among pathology parameters, an adverse prognosis was correlated with a high Ki-67 labeling index and EBV DNA load but not with cellular morphology or the expression of CD56.…”

TH9 cells in skin disorders

“…IL-9 has long been recognized as an important growth and differentiation factor for transformed lymphoid cells, including malignant T cells [58–61]. In addition, IL-9 is also capable of modulating the inflammatory microenvironment of lymphoid tumors [62].…”