Abundant expression of interleukin-21 receptor in follicular lymphoma cells is associated with more aggressive disease

Abstract

Recombinant interleukin-21 (IL-21) has potential utility in cancer therapy. Stimulation with IL-21 can induce apoptosis in follicular lymphoma (FL) cells, and existing studies have suggested that IL-21 signaling may function in tumor suppression. In order to elucidate the relationship between IL-21 receptor (IL-21R) expression and clinical and pathological features in FL, IL-21R was quantified in 114 pretreatment biopsy samples using either conventional immunohistochemistry or immunofluorescence microscopy and automated quantitative analysis (AQUA). Reduced expression of IL-21R was associated with favorable overall survival (p = 0.048). AQUA analysis showed an association with the presence of diffuse large B-cell lymphoma (DLBCL) in the biopsy sample (p = 0.03), and expression of IL-21R was up-regulated upon transformation of FL to DLBCL in two cases. Our results based on the largest survey to date raise the possibility that IL-21 signaling in FL cells, rather than being tumor suppressive, supports tumor progression and that therapeutic benefit could be realized by blocking IL-21R instead of stimulating it.

Keywords::

• Follicular lymphoma
• interleukin-21
• immunofluorescence
• AQUA
• prognosis
• cytokine

Acknowledgements

The authors thank Mr. Lee Boudreau and the Queen's Laboratory for Molecular Pathology for technical assistance. This work was support by a grant to D.P.L. from the Leukemia & Lymphoma Society of Canada. The contribution to this work by A.A. was supported by a scholarship from the government of Saudi Arabia.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.