Th-17/IL-17 Axis in Chronic Lymphocytic Leukemia

• Published in: Blood 2009-11, Vol.114 (22), p.2357-2357
• Main Authors: Jain, Preetesh, Yan, Xiao J., Javdan, Mohammad, Chiu, Pui Yan, Damle, Rajendra N, Kothari, Tarush, Allen, Steven L, Kaufman, Matthew, Kolitz, Jonathan E., Rai, Kanti R., Chiorazzi, Nicholas, Sherry, Barbara
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.2357.2357

Abstract 2357 Poster Board II-334 Maintenance of chronic lymphocytic leukemia (CLL) clones is dependent on complex interactions between leukemic cells and soluble factors released by cells within the microenvironment of the blood, bone marrow, lymph node and spleen. Studies in our laboratory demonstrated elevated levels of IL-17, a pro-inflammatory cytokine secreted by a subset of CD4+ effector T cells (Th17 cells), in the sera of CLL patients as compared to those of healthy age-matched subjects. We hypothesized that the Th17/IL-17 axis is active in CLL, creating a proinflammatory microenvironment that promotes growth and angiogenesis. To test this hypothesis, we analyzed the expression of both IL-17 and IL-17 receptors in blood, spleen, and lymph nodes of CLL patients and normal control subjects. All studies involved patients with CLL and healthy subjects matched for age. Constitutive and inducible intracellular IL-17 expression was assessed in cryopreserved peripheral blood mononuclear cells (PBMCs) isolated from untreated CLL patients (n = 27) and healthy individuals (n = 8). Flow cytometric analyses were performed at baseline (Day 0) and after 7-day culture with or without the Th17-polarizing cytokines, IL-1b and IL-23. Surface expression of IL-17 receptors A (IL-17RA) and B (IL-17RB) was analyzed on PBMCs of CLL patients (n = 25) and healthy controls (n = 8) using flow cytometry. Lastly, IL-17 expression was assessed by immunohistochemistry in spleen and lymph nodes from CLL patients and healthy subjects. Intracellular analysis of IL-17 expression in PBMCs revealed a higher median percentage of CD4+ Th17 cells in CLL patients (Median=0.73; range: 0.0-3.6%) compared to healthy subjects (Median=0.13; range: 0.0-0.8%) at baseline; this was a statistically significant difference (P2% and CD38low